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PN Issue 107 / Summer 2017 News

Open science movement The war to liberate knowledge Future Physiology 13 - 14 December 2017 Leeds, UK

A two-day scientific and career development conference organised by early career physiologists. www.physoc.org/futurephysiology

Physiology News Editor Roger Thomas We welcome feedback on our membership magazine, or letters and suggestions for (University of ) articles for publication, including book reviews, from our Members. Editorial Board Please email [email protected] Karen Doyle (NUI Galway) Physiology News is one of the benefits of membership, along with reduced registration rates Rachel McCormick for our high-profile events, free online access to our leading journals,The Journal of Physiology, (University of Liverpool) and , and travel grants to attend scientific Graham Dockray meetings. Membership offers you access to the largest network of physiologists in Europe. (University of Liverpool) Keith Siew Join now to support your career in physiology: () Visit www.physoc.org/membership or call 0207 269 5721 Austin Elliott () Mark Dallas (University of Reading) Membership Fees for 2017 FEES Fiona Hatch Fellow £120 (Cello Health Communications iScience, Medical writer) Member £90 Managing Editor Retired Member – Julia Turan YOUTUBE LOGO SPECS Affiliate £40 [email protected] PRINT on light backgrounds on dark backgrounds Associate £30 standard standard main red gradient bottom PMS 1795C PMS 1815C www.physoc.org C0 M96 Y90 K2 C13 M96 Y81 K54 Undergraduate –

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2 Physiology News / Summer 2017 / Issue 107 Contents

Welcome to the Summer 2017 edition of Physiology News

Introduction Meetings & events

05 Editorial 20 Forthcoming events IUPS: the Two-way Physiology Street and the Mutual Benefits of Volunteering Expertise 21 British Association 2017 Festival of Neuroscience News in brief Our Workshop: Introduction to Molecular Techniques, Transfection and Functional Studies 06 Reports of recent Committee Meetings 22 H3 Symposium: Practical Innovations in the Life Sciences 07 Physiology Feed 23 From the Archives 08 First group of Members awarded Fellowship Getting excited about pacemaking in the athletic heart, the first R Jean Banister Prize Lecture 09 Policy Focus Features

24 The open science movement 30 Cortisol: often not the best indicator of and poor welfare News in depth 33 Science and politics 10 Journal updates 36 What does the future hold for research into Epithelia & Membrane Transport? 12 The membership survey results are in! 38 Stressing out the immune system 14 Belief, science and facts 16 Stressed-out Britain? 18 Introducing our MOOC in Physiology 19 Reddit ‘Ask me Anything’ (AMA) with Kim Barrett Membership 42 The dangers of careless press releases 43 The Society welcomes our new Treasurer, Frank Sengpiel 44 How many Members of The Society have won the ? 49 Obituaries

Cover image: This work is a derivative of ‘ Explained!’ [https://www.youtube.com/watch?v=L5rVH1KGBCY] by ©PhDComics.com Licensed under CC BY. Read the first of our two-part series about open science on p. 24. 3 Annual General Meeting 2017 Wednesday, 12 July from 14.30 Wellcome Collection, London, UK All members can attend, only Full and Honorary Members can vote

More information at www.physoc.org/agm-2017 Editorial

this year it will be held in the Wellcome I have already participated in a meeting of Roger Thomas Collection nearby. It is remarkable how few the PCC, but only via telephone. This was my Editor meetings, if any, are now held in Universities, first experience as a teleconferencer rather when not so long ago they almost all were. than as chairman of a meeting with one or One reason, I suppose, must be the multiplication two members phoning in, and I was not of suitable conference centres, which undertake always able to work out who was talking. I This issue of Physiology News is full of all the arrangements previously left to the look forward to reading the minutes so I will interesting material. The long and thoughful hosting departments. Sadly, such venues understand what we all agreed. I complained article by Keith Siew about aspects of the rather rule out any demonstrations, which for about the excessive use of acronyms in the open science movement (part 1, part 2 will many were the highlight of meetings of The minutes of the previous meeting, held before be in the next issue, written by Vivien Rolfe) is Society. I was myself the local organiser of I was an ex-officio member. very thought-provoking. Of course, prestigious several Society meetings in , one journals such as The Journal of Physiology are involving a train ride to Bath for the meeting As the exam season is now upon us, I am not at first ‘open’, since subscribers have to dinner in the pump room. I suppose my efforts reminded again of my personal doubts about pay. The Society does benefit considerably. were all rather time-consuming and irrelevant whether the UK method of examinations for There is an intriguing article by Tilli Tansey to the Research Assessment Exercise. But I do biology-related subjects is fit for purpose. about physiologist winners of the Nobel Prize. miss the opportunities to see what is going on How important in real life is it to be able to Many Nobel laureates were Members before in other physiology laboratories. write essays on a relevant topic with no winning, others were only elected afterwards. access to any notes, books or the internet? Universities like to boast about winners who Members may be interested to know that The current system rewards good memory studied there, even if their research was done oversight of Physiology News has passed to rather than any real understanding of the elsewhere. There is also a fascinating article the Policy Committee of The Physiological subject being examined. I understand that the on the 1923 International Congress, held in Society, which has been renamed the Policy Italian system is quite different, with mostly Edinburgh. It was too soon after the First and Communications Committee (PCC). The oral exams, but of course it still rewards a World War for some Europeans to feel able to change was discussed and agreed by all of good memory. This may be even more attend. There are also two articles about Council, and also agreed by the PCC committee stressful than four sessions of writing three aspects of stress, and there will be more in and the Chair of Publications Committee. PN essays in three hours, and the lack of paper PN 108. was previously seen as a publication and was evidence may lead to accusations of thus overseen by PubComm. I am happy with favouritism. It does avoid the problem of poor If all goes well, this issue should appear just this new arrangement. To be fair, PubComm is handwriting at least. The big advantage of the before the IUPS congress in Brazil, which concerned with peer-reviewed journals, and UK system is that it’s hard to cheat as long as replaces The Society’s normal main summer PN cannot be so described. It did start life as mobile phones and similar technology is meeting. I have been to several IUPS Committee News, and I am pleased that it will eliminated from the exam venue, but reading congresses, most memorably in Sydney, but I now include more reports from The Society’s and assessing great piles of essays is cannot make it to Rio de Janeiro. I hope all who many committees. It has taken me over a year extremely taxing for the examiners. I attend have a great time. We remainers in the to persuade some of the various committee earnestly hope that soon some way will be UK will have the consolation of an exciting chairs to supply such information. When found to allow candidates to use word- Annual General Meeting (AGM) in London at Committee News was launched in 1983, The processors. Medical student handwriting is 14.30 on 12 July. The AGM will be followed Society had only the one committee; now it often appalling. by 2 hours of selected Affiliate presentations has 12 if I include the Council of Trustees. - flash oral communications and posters. After Admittedly there were various sub-committees that there will be a President’s Lecture and a in earlier days. Actual membership of The reception. When I joined The Society, the AGM Society has perhaps only doubled over the was always held in University College London; same period.

5 News in brief

Reports of recent Committee meetings

The purpose of these short updates is to keep structure of the committee to identify areas The use of to engage the Affiliate you informed about the inner workings of our in which we could strengthen its membership. membership was the next point of discussion. Committees. The following summaries detail If you have an interest in contributing to our It was agreed that more could be done, but the meetings of the past few months. work with research funders or to our external the question is more of what? Managing a communications, we’d like to hear from you. social media account is no small task, so it was agreed that an Affiliate-focused newsletter History & Archives We have recently released several reports on would be a good way to establish regular our activities, including our events at last communication. If any Affiliate Members have Committee year’s party conferences, a YouGov survey ideas, we’re all ears! about stress, a membership survey about Several topics recently discussed by the Brexit, and the report on the PCC/Education With this in mind, all members felt regular History and Archives Committee (HAC; and Outreach joint meeting on the Teaching columns in Physiology News would be a good chaired by Graham Dockray) have already Excellence Framework, in partnership with idea to improve membership engagement. It been covered in PN. For example, the last Universities UK. We also contributed to the was agreed after discussion with the PN issue contained a piece by David Miller on AV recent HEFCE consultation on REF2021. Editorial Board that the AWG will guest edit Hill’s Nobel Prize Diploma (PN 106, p.12–13): issue 109 later this year, which members HAC has debated the most appropriate way The In Vivo sub-committee, chaired by Andrew should receive shortly before the Future to represent the diploma at H3. Should we Trafford, continues to work with the UK Physiology meeting. display the original diploma (given that it is Bioscience Sector Coalition in meetings with unique there are security and insurance issues the Animals in Science Regulation Unit (ASRU). Full details of the AWG can be found online at here)? Should we produce a facsimile for Currently, ASRU is looking at the process and www.physoc.org/affiliate-working-group display, and if so should it be a copy of the form of the PPL, hosting stakeholder meetings whole diploma, front and back, or just the around the UK. Our Members have been main part? Should it be on a wall or in a contributing to this process, meeting with display cabinet? Before long, visitors to ASRU in January and March in preliminary Hodgkin Huxley House should be able to see discussions, and contributing to these the outcome of these discussions. on-going stakeholder consultations. Education & Outreach

Oversight of The Society archives is a major Committee part of the HAC remit. The last issue of PN (106, p. 10–11) contained a piece by The main points of business at the Education Georgina Lever describing her work on the and Outreach Committee meeting in April, accrual of the latest batch of archives, which Affiliate Working Group chaired by Sarah Hall, included an update on is something that is done every 5 years. The the progress of the new Physiology Massive archives provide a research resource that, for Committee Open Online Course (MOOC), and a report on example, was used by Tilli Tansey for her piece the impact evaluation of the Vacation in this issue of PN, page 44. The second meeting of the newly formed Studentship scheme. The Committee met Affiliate Working Group (AWG) was held at 3H with the project team that is leading on the The 150th anniversary of the founding of The on 22 March 2017. As the Society’s Annual development of our MOOC, which will be an Society will occur in 2026. The development General Meeting (AGM) will be held in London introductory course aimed at 16 to 19- of a strategy on the part of HAC to meet the (on 12 July), and will not be part of the main year-olds to encourage them to consider challenge was the focus of a special meeting meeting in Brazil, it was decided there will be studying physiology at university. in January. A number of relevant projects have several talks and presentations around the been initiated including enhancement of open meeting, some of which will be delivered by General feedback regarding content was access resources on our own website. our Affiliate Members. All members of the given to the team from the University of AWG agreed that a mixture of oral and poster Liverpool, which is developing the MOOC in presentations would work well, with the partnership with The Physiological Society addition of a prize for the best of each. and FutureLearn. The Committee also recommended potential avenues for The AWG is also actively involved in advertising the MOOC to its core Policy & Communications organising Future Physiology demographic. Enrolment on the course will www.physoc.org/futurephysiology, open this summer. Read more on page 18. Committee our first multi-day conference dedicated to early career researchers. The conference, The Committee was very pleased with the The Policy and Communications Committee happening in Leeds in December, includes responses presented from a recent survey of (PCC, ex-Policy Committee, chaired by Lucy invited presentations by early career and past Vacation Studentship awardees during Donaldson) is working on several projects at senior researchers, oral and poster 2013–2015: 84% of respondents are still in the moment. Of note for The Society’s presentations, inspirational talks, and career academia, 60% of whom are doing what they Members is that we are looking at the development workshops. consider to be physiological MSc, PhD or

6 Physiology News / Summer 2017 / Issue 107 Physiology Feed postdoc research, and 100% said the Vacation together with another proposal, would make Studentship had a positive impact on their for a good combined event. Support for career plans. A full report of the survey international meetings in 2017 will be given Bringing you snippets of the latest findings will be published inPN 108. to the 37th PSN Conference in Kaduna, intriguing research Nigeria, as part of our remit to enhance the communication of physiology both nationally and internationally. Therapeutic vaccine controls HIV without drugs

On a more general note, re-forecasting of The immune systems of five HIV+ patients Membership & Grants budgets (where necessary) and a review of treated with two vaccines and the cancer registration fees for events taking place in drug romidepsin were able to suppress the Committee 2019 and beyond, to enable widespread virus unaided. The therapeutic vaccine is a participation from all physiologists, regardless treatment for people already infected with Tasked with leadership of The Society’s of career stage, will be carried out. The HIV as opposed to preventative immunisation, membership strategy and grant oversight, the Society will be drafting a form for the online and is the first to stop the virus from Membership & Grants Committee held the submission of proposals for topic meetings replicating without the use of daily drugs. first of their bi-annual meetings this April, and H3 symposiums. Lastly, Sue Deuchars has chaired by Rachel Tribe. replaced Ken O’Halloran as Chair of the bit.ly/2kTzTxU committee and will continue in this role until The agenda covered membership reporting, the 2018 AGM. Unlimited blood supply grant impact reporting and developments to the newly installed customer relationship The first human immortalised erythroid management (CRM) system. A member of line (Bristol Erythroid Line Adult or BEL-A) the Affiliate Working Group attended to can generate functional red blood cells in discuss matters relating to Affiliates, and to vitro for clinical use sustainably and scalably. update on planning for Future Physiology. Also Publications Committee DOI: 10.1038/ncomms14750 discussed was the launch of Fellowships and the unfortunate delay with getting the first The Spring Publications Committee was held round of applications approved. With the on May 4 2017 and chaired by Prem Kumar. Repurposed drugs prevent technical delay to be resolved shortly after neurodegeneration the meeting, the Committee were confident Since the last meeting, a new long-term those applicants waiting on a decision would publishing contract with Wiley for Trazodone, a licensed anti-depressant, and be notified soon. Experimental Physiology and The Journal of dibenzoylmethane (DBM), a compound Physiology has been signed. being trialled as an anti-cancer drug, have The Committee also heard the initial highlights both been found to prevent from the 2017 membership survey, which The Editor-in-Chiefs (EiCs) of Experimental in prion-related disease and improve had closed 2 days before. The results of this Physiology and The Journal of Physiology memory tests for other neurodegenerative diseases in mice. survey will feed into the Committee’s planning have continued to implement their strategic over the next 18 months, ensuring our plans for the journals. Mike Tipton, EiC of DOI: 10.1093/brain/awx074 activities are geared towards the needs of the Experimental Physiology, has restructured membership. Further insight from the survey the Editorial Board, with one new Senior can be found on page 12. Editor and 44 Reviewing Editors being Salt makes you hungry not thirsty appointed. Kim Barrett, EiC of The Journal of The assumption that high salt intake Physiology, is improving the evenness of increases drinking has been turned on its coverage across physiology and is particularly head by two new studies. Long-term high pleased to have appointed new renal and salt diets in humans and mice increase endocrine Reviewing Editors, Dennis Brown hunger and reduce water intake despite and Fiona Gribble. The number of direct Meetings Committee increased urine volume. This is due to submissions for Physiological Reports has -induced breakdown of the Plans are progressing for Europhysiology gone up, with the overall number of body’s fat and muscle which generates 2018, and discussions are under way submissions increasing too. The Joint surplus water. regarding the events in 2020 and 2022. Management Board is in the process of appointing the new EiC, to take over when DOI: 10.1172/JCI88530 Looking ahead to The Society’s next main Sue Wray steps down at the end of the year. DOI: 10.1172/JCI88532 meeting, taking place in 2019, the

Committee is currently considering three Wiley provided a publisher’s report for each potential Scottish locations for this. There are journal, showing that article downloads are Short-term memories don’t several topic meetings in the pipeline increasing. become long-term memories including ‘Mitochondria – Form and Function’, Contrary to the standard theory of memory which takes place in London on 14–15 Ken O’Halloran has stood down from the consolidation, which says that you gradually September 2017, and the organising Publications Committee, and Sue Deuchars as transfer the memories, optogenetic committee for ‘Experimental Models in the interim Chair of Meetings Committee, has studies have discovered that long-term Physiology’ (planned for 2018) will shortly be replaced him as an ex-officio member. memories develop at the same time as finalising the programme for this event. The short-term memories, only staying quiet H3 symposium on ‘The Integrative Physiology while they mature. of Physical Inactivity Across the Lifespan’ was approved, and it was deemed that this, DOI: 10.1126/science.aam6808

7 • Kim Barrett, University of California • David Paterson, University of First group of • Angus Brown, University of Nottingham • Susan Pyner, University of Durham • Marco Canepari, National Institute of • Andrew Randall, University of Exeter Members awarded Medical Research • Richard Ribchester, University of Edinburgh • Gordon Cooper, • Alexey Semyanov, Institute of Fellowship • Susan Currie, University of Strathclyde Neuroscience Russia • Timothy Curtis, The Queen’s University at • Luis Sobrevia, Pontificia Universidad In January of this year, The Society launched Belfast Católica de Chile its new membership category of Fellowship, • Brian Day, Institute of Neurology • Rachel Tribe, King’s College London to enable Members to demonstrate career • Mary Diaz, University of Edinburgh • Jeremy Ward, King’s College London progression, professionalism, and • Jack Feldman, University of California • Michael White, University of commitment to physiology and The Society. • Stuart Galloway, University of Stirling • David Wyllie, University of Edinburgh • Simon Gandevia, Neuroscience Research • Alexander Zholos, Kiev National The review panel, members of the Australia Shevchenko University Membership & Grants Committee, were • Carolyn Greig, impressed with how well the applicants • Patrick Harrison, University College Cork The Trustees of The Society congratulate demonstrated wide engagement with The • Christopher Johnson, The Queen’s these members on their achievement. Society’s activities. Those elected to University of Belfast Fellowship are as follows: • Andrew Jones, University of Exeter Full details can be found here: • Andrew King, www.physoc.org/fellow-membership • Damian Bailey, University of Glamorgan • Peter Kohl, University Heart Centre • Deborah Baines, St George’s London • Ken O’Halloran, University College Cork

Getting excited about pacemaking in the athletic heart, the first R Jean Banister Prize Lecture

fundamental to our modern understanding of In the R Jean Banister Prize lecture I present pacemaker , the current evidence demonstrating that the focus of my research. And thus, for transcription factor NKX2.5 upregulates engineering a connection to the historical microRNA-423, causing downregulation of greats in the field, I am forever indebted to the pacemaker channel HCN4 and sinus The Society. bradycardia in the athletic heart. I also present novel evidence that the core circadian clock I received my PhD in 2011 studying structural transcription factor BMAL1 drives a rhythmic remodelling in diabetic cardiomyopathy with circadian variation in HCN4 and ultimately Jaipaul Singh at the University of Central intrinsic heart rate, explaining an increased Lancashire. It was at this time that my interest incidence of nocturnal bradyarrhythmias, in electrophysiology was piqued, and I also known to be more frequent in the subsequently moved to The University of athlete. We are delighted that our work has Manchester to investigate exercise-induced received prominence through publicity in the arrhythmogenic cardiac remodelling with popular media and awards including a Mark Boyett. shortlisting for the GW Mendel Medal at ‘SET for Britain’ (now called STEM for Britain) Veteran athletes are prone to cardiac in 2013, the 2014 International Society for arrhythmias including sinus bradycardia, Heart Research/Servier Fellowship Prize and heart block and atrial tachyarrhythmias but the 2016 Cairn Electronics ‘New and the underlying mechanisms are poorly Notable’ award. Alicia D’Souza understood. Our work in mice has shown that training-induced sinus bradycardia and I am filled with enthusiasm for the future, as University of Manchester, UK first-degree heart block, the most common we continue to identify key players in rhythm disturbances in athletes, are due to training-induced electrical remodelling and diffuse downregulation of pacemaking ion work with clinical colleagues towards It was a tremendous compliment to receive channels in the sinus and atrioventricular translating these findings into small molecule the inaugural award. Much more so, once I nodes. Delineating the transcriptional therapies for arrhythmias in the athlete. learned about the life and work of Jean ‘switch’ that produces this phenotype could Within the broader remit, I envisage that our Banister from one of her former pupils, Hilary lead to new targets for managing future studies may reveal novel therapeutic Brown. What really struck a chord is that Jean arrhythmogenesis in athletes and hence our strategies for other pathological conditions Banister’s former mentees (including Hilary focus is on upstream control mechanisms where ion channels are dysregulated, e.g. Brown, Susan Noble, Wayne Giles and Dario with specific emphasis on microRNAs and atrial fibrillation and heart failure. DiFrancesco) went on to discover concepts transcription factors.

8 Physiology News / Summer 2017 / Issue 107 Policy Focus Physiology Feed

Bringing you snippets of the latest Henry Lovett intriguing research Policy and Public Affairs Officer, The Physiological Society Bioengineered pancreas replaces insulin injections Members’ views on Brexit A year after transplanting insulin-producing islet cells into the omentum of a woman with Brexit could be called the elephant in the room, but it is dominating political attention even type 1 , the cells continue to function more than the average pachyderm. It is the elephant, bedecked in flashing lights and wailing and have restored stable glycaemic control klaxons, in the room. The Society recognises that Brexit could have significant effects on the without the need for exogenous insulin. life and work of scientists, and so sought to understand our Members’ opinions on the critical DOI: 10.1056/NEJMc1613959 elements of any Brexit process. The 350 responses to our survey conducted earlier this year give a detailed picture of the issues that matter. Key points included: What makes people reject • Fundamentally, physiologists voted heavily to remain in the EU (85%). science? Psychological meta-analysis studies have • Movement of people was seen as the most important single issue of the campaign (34%). found that people who reject scientific consensus are generally just as interested in • Free movement for scientists and students (42% combined) is seen as a bigger key goal for science and as well-educated as the rest of Brexit negotiations than EU funding access (33%). us. However, people cherry pick studies that back up prior-held beliefs, or in other words • That said, there are significant concerns about funding, with 61% of respondents thinking – cognitive bias. A big part of the growth in their research funding will be reduced by Brexit. science denial is that people now associate scientific conclusions with political or social • Of those respondents whose opinion on the outlook for science after Brexit has changed affiliations due to a polluted science since the result, 78% think it has got worse. communication environment. To convince people, avoid directly taking on surface • Large numbers of respondents (approx. 20% across different issues) have already attitudes and instead tailor messages to experienced problems related to international collaborators or EU staff, and even more align with their underlying . expect problems in the future. bit.ly/2j9r79u The science sector has been vocal in communicating its concerns around Brexit to policymakers. However, it seems our efforts must be redoubled, because 52% say there has not been enough Bones are endocrine organs activity from the sector in response to the leave vote. Researchers have shown that a View the full results of the survey as an infographic here: bit.ly/brexitsciencesurvey secreted by bone, called lipocalin 2 (LCN2), suppresses appetite. Osteoblast-specific LCN2 knockout mice have 67% lower circulating levels of LCN2, eat more and show increased fat mass and body weight

DOI: 10.1038/nature21697

Higher Education & Research Bill becomes Using ‘poo’ to extend lifespans Middle-aged killifish receiving young gut law in parliament’s last-minute rush microbiome transplants extended their median lifespans by 41% compared to fish With the unexpected announcement by Theresa May of a snap election, a hard deadline was exposed to microbes from middle-aged slammed down in front of all legislation going through parliament. If it could not be passed animals, and lived 37% longer than fish that before dissolution for the campaigning period, it would cease to exist. This frantic period of received no treatment. trying to pass outstanding legislation is known as the ‘wash-up’. It tends to require significant DOI: 10.1101/120980 compromises from the government in order to prevent Bills being blocked until it is too late. This was the case for the Higher Education and Research Bill, which had been due to have significant Lords’ amendments return to the Commons chamber. How Sherpas overcome hypoxia In a comparison between lowlanders and The final form, now the Higher Education and Research Act 2017, mostly follows the Himalayan Sherpas making the ascent to government’s agenda as planned, with the formation of UK Research and Innovation as an Everest Base Camp, researchers found umbrella body overseeing the Research Councils, the Office for Students replacing Hefce, and Sherpas’ mitochondria were more efficient the Teaching Excellence Framework (TEF) rating universities’ teaching quality. However, at producing ATP and had lower levels of fat significant concessions mean the TEF will not be linked to differential fee increases until at least oxidation, suggesting they were better at 2021 (with across-the-board increases with inflation allowed instead). Additionally, the generating energy from sugars, which is a opening of the higher education market to new ‘alternative providers’ will now require less -hungry fuel source. additional quality assurance stages. With a few other small changes, the Bill was deemed acceptable by the Commons and Lords and has received royal assent. DOI: 10.1073/pnas.1700527114

9 Journal updates EP at IUPS

The Editor-in-Chief (Mike Tipton) and Reviews Editor (Jeremy Ward) of Experimental Physiology selected the following Symposium from the IUPS Meeting programme for sponsorship:

SYMPOSIUM 16 – Autonomic Rhythms in Health and Disease

• Susan Deuchars (Chair, UK) – Changing levels of rhythmic sympathetic nerve activity Top 10 referees in 2016 • Song Yao (Australia) – Blood-brain barrier and autonomic rhythms Experimental Physiology (EP) would like to thank all of the people • Ruth Stornetta (USA) – Pre-sympathetic C1 neurones: a nodal who submitted reviews over the last year. In particular we would like point for stress? to thank our top ten referees (those listed have agreed to be named): • Alex Gourine (UK) – Glial control of autonomic circuits

• Louise Deldicque • Rachel C Drew Subject to submission/review, reports from this symposium will be • Timothy Etheridge • Wim Lammers published in Experimental Physiology following the meeting. • David Low • E Matthew Morris • Nathaniel Szewczyk • Can Ozan Tan

Early Career Author Prize winners

The Early Career Author Prize of $1000 (for articles published in 2016) was awarded to Havovi Chichger, Anglia Ruskin University, for ‘Experimental type II diabetes and related models of impaired differentially regulate glucose transporters at the proximal tubule brush border membrane’. 2016 Early Investigator Prize

Brittany A Edgett of Queens University, Canada, winners announced! received the runner-up award of $500 for ‘SIRT3 gene expression but not SIRT3 subcellular The winners are Calum Wilson and Matthew D Lee for their paper localization is altered in response to fasting and ‘Acetylcholine released by endothelial cells facilitates flow-mediated exercise in human ’. dilatation’.

The two runners-up are Matthew S Brook for his paper ‘Synchronous deficits in cumulative muscle protein synthesis and Case Studies ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans’, and David G S Farmer for his paper ‘Brainstem Case Studies providing a perspective on one-off cases and individual sources of cardiac vagal tone and respiratory sinus arrhythmia’. presentations in both humans and animals may now be submitted to Experimental Physiology for consideration. The winners will share a prize of $1,000 and the runners-up each They must have a physiological focus and adhere to the journal receive a $500 prize. policy for human and animal experiments. As these are likely to be studies of exceptional individuals or cases they can provide unique We are thrilled that Calum also won and revealing insights that other papers do not. the 2015 prize, which is testament to the great work he is doing at the Editorial Board update University of Strathclyde! Winners Calum and Matt

We welcome Peter Rasmussen to the Experimental Physiology board as Reviewing Read up on our latest CrossTalk Editor in the area of human/environmental and . debate!

Paula Rodriguez-Miguelez, Melissa L Erickson, Kevin K McCully and Ryan A Harris argue that ‘Skeletal muscle oxidative capacity IS EP at Experimental Biology altered in patients with cystic fibrosis’, whereas Erik Hulzebos, Jeroen A L Jeneson, Cornelis K van der Ent and Tim Takken believe Experimental Physiology held an Editorial Board at The Experimental that oxidative capacity IS NOT altered in cystic fibrosis patients. Biology annual meeting in Chicago. We also hosted an extremely well-attended Meet the Editor(s) session where delegates were able to meet the Editors whilst drinking beer and eating pizza. Read our CrossTalk debates here: bit.ly/CrossTalkDebates

10 Physiology News / Summer 2017 / Issue 107 Recently published special issues

K+ channels and cardiac electrophysiology Volume 595, issue 7 – April 2017

Biomedical basis of elite performance New Editorial team Volume 595, issue 9 – May 2017 At the end of the year, Physiological Reports will reach another landmark when Sue Wray, the founding Editor-in-Chief, stands down after 5 years at the helm. Advances in calcium signalling Anyone who has encountered Sue in this Volume 595, issue 10 role will appreciate the ambition, creativity – May 2017 and hard work that she has brought to it. A few arms have been twisted (with a Cardiac regulatory charming smile, of course) along the way mechanism but only where absolutely necessary. Volume 595, issue 11 – Unquestionably, the success of the June 2017 journal is very largely down to the drive of Sue and her editorial team. Sue Wray and Tom Kleyman

The Joint Management Board (JMB; joint, that is, between The Call for papers! Society and the American Physiological Society) was tasked with finding Sue’s successor. There was strong competition for the The Journal of Physiology is delighted to announce that it will be position. In the event, the JMB appointed Tom Kleyman of the publishing a special issue dedicated to recent advances in cellular Department of at University of Pittsburgh. Tom has served and integrative control of oxygen and . as Deputy Editor-in-Chief of Physiological Reports since its launch and is a former Editor-in-Chief of AJP: Renal Physiology. This call for papers is linked to the XX Meeting of the International Society of Arterial Chemoreception (ISAC) (23–27 July 2017, The new Deputy Editor-in-Chief will be Professor Morten Bækgaard John Hopkins University, Baltimore, MD, USA). Thomsen of the Department of Biomedical Sciences at University of Copenhagen. Morten works on cardiac arrhythmias and heart The Journal of Physiology is seeking the submission of original failure, and is currently an Associate Editor of Physiological Reports. articles covering the full scope of oxygen and carbon dioxide homeostasis, from the cellular level to the whole . We look forward to the journal’s continued development and growth Examples may include but are not exclusive to the following topics: under the editorship of Tom and Morten.

• Molecular responses to hypoxia and hypercapnia

• O2/CO2 sensing in the carotid body First formal citation metric

• O2/CO2 sensing in the brain Physiological Reports has taken another step forward in receiving its • Polymodal properties of arterial chemoreceptors first formal citation metric. Without going into the technicalities, • Adaptive and maladaptive responses to chronic or intermittent CiteScore is a new metric based on Scopus citation data. It is hypoxia calculated in much the same way as , but with a longer • Role of chemoreception in disease window of cited papers (3 years’ worth rather than 2 years) and including all types of article rather than only research and review The following speakers from the meeting have agreed to contribute papers. The 2016 CiteScore for Physiological Reports is 0.69. to the special issue:

• Cormac Taylor, University College, Dublin • Christopher Wyatt, Wright State University, USA • Jay Nanduri, University of Chicago, USA • Rodrigo Iturriaga, Pontificia Universidad Católica de Chile • Michael Joyner, Mayo Clinic, USA • Andrea Pozionato, University of Padova, Italy • Camillo Di Giulio, University of Chieti, Italy • Patrice Guyenet, University of Virginia, USA • Nino Ramirez, Seattle Children’s Hospital, USA

Deadline for submissions is 30 September 2017. Contact Managing Editor Sally Howells ([email protected]) for more information!

11 News in depth Breakdown of respondents by profession:

Undergraduate study

3 Masters students 0 33 16 Breakdown ofThe0 respondents membership by profession: survey results are in! 7 PhD 12 72 UndergraduatePostdoc study

3 Membership Masters students The results included research funding Jen Brammer Technician/Labenvironment manager (79%), higher education policy 0 16 0Membership 33 Engagement Manager, Members were asked to indicate the benefits (69%) and raising the profile of physiology The7 Physiological Society they most value, providingPhD insight into the amongst policymakers (47%). Members reasons why people join, but also whyAcademic they reported researcher that they contribute - scientist to science 12 remain. World-class scientific meetings policy debate through their institution or 72 ranked highest with Postdoc63% of the votes, company. Interestingly, 38% of respondents Conducted biennially, the recent Membership opportunities to present research cameAcademic do not researcher engage with policy - clinician debate. The Survey provided an opportunity for you to second with 52%32 andTechnician/Lab networking managerPolicy team of The Society are keen to share your views on The Society, what it is opportunities closely behind in third with(including reduce vets this figure. doing well, what we need to improve, and 51%. Career development and mentoring what is important to you. These results were key opportunitiesAcademic that respondents researcherClinically said - Meetingsscientist employed & events (including directly feed into our strategic and would add more value to membership.vets) operational planning, to ensure The Society Respondents gave very positive reasons for 2 Academic researcher - clinician and the183 support we offer our members Support32 for Affiliate members was highlightedCommercially attending employedThe Society’s meetings and this remains current. as an area where progress(including has been vets made, reflects the efforts of our Event Managers with respondents favourableClinically of initiativesemployed (includingwho provide high-level engagement through We will share an executive summary of the introduced so far. There were also a lot of top-quality programmes. Hearing about vets) Teacher responses with all Members, but until then new2 ideas suggested as well, which will feed cutting-edge research ranked highest with here183 are some highlights. into the work of the CommerciallyAffiliate Working employedGroup. 76%, opportunities to present was second Retired withacademic 65% and networking or clinician opportunities was Approximately 13% of Members responded, Policy third with 64%. For those organising their which is less than anticipated, but this still Teacher own scientific meetings, the results highlight provides really useful data as those who Respondents were asked to select their top an appetite for marketing and meeting replied provided a real insight into the feeling three areas they feltRetired The Society academic should or clinicianplanning support. and needs of the membership. focus on in its policy activities. The top three results reflect the current environment and Education & outreach key concerns for Members. Members value engaging the public with Composition of respondents by member type: their research, with 67% carrying out activities involving the public. Engagement Composition of respondentsComposition of respondentsby member by type:member type with schools and children was lower (31%) with a lack of support or resources to do this cited as barriers. Respondents suggested that partnership opportunities (45%) and 17 20 16 personal development skills training (46%) 42 Honorarywere key areas where The Society could Honorary better support engagement activity. Retired 73 Retired Communications Full Member Member Full MemberMembers are happy with the monthly newsletter with 46% saying they found it AffiliateAffialiate Affiliateuseful and the content pitched at the right level. 34% of respondents use social media to Associate keep up to date with the latest published Associateresearch, with 75% expecting to see the Undergraduate latest Physiology News in The Society’s social 220 Undergraduatemedia content. On the website, Members would be interested in more information about meetings and events, general research news and theme-focused news. Actual composition of membership at time of survey: 12 Physiology News / Summer 2017 / Issue 107 Actual composition of membership88 at time of survey:

567 370 56 88 Honorary Retired 567 370 56 Full Member Honorary Affiliate Retired 907 Associate 1544 Full Member Undergraduate Affiliate 907 Associate 1544 Undergraduate

PerceivedPerceived valuevalue ofof Member member benefits benefits:

70%70% NetworkingNetworking opportunities opportunities 63%

60%60% AccessAccess toto education education resources resources

51% 51% CareerCareer development/development/training 50%50% opportunitiestraining opportunities

AccessAccess toto the the most most up-to-date up-to-date science 40%40% science FeelingFeeling part part of of a acommunity community

30%30% WorldWorld-class class scientific scientific meeting

20%20% OpportunitiesOpportunities to to present present your your research research

ComplimentaryComplimentary journal journal 10%10% subscriptionssubscriptions GovernmentGovernment and and science science policy policy influenceinfluence 0%

PhysiologyReasons News for attending our meetings:

The content of the magazine was highly rated. ‘News in brief’ was most popular (85% Raise The Society’s profile and support responded good or very good). Reading the magazine in print remains the most popular 40% your colleaguesHearing cutting edge with membership! choice of members (44%), with 27% opting research for a combination of in print and online. 75% As a Member, there areOpportunities several ways to presentsomeone representing The Society to Equality & diversity to engage with us and our activities attend or providing marketing material. and to help you make the most of your The Society’s commitment57% to strengthening membership. One wayNetworking is to become a Reps also have the chance to attend practices in diversity, quality and inclusion Society Representative (Rep). Our growing operational and best practice focused has made great progress since the signing of network of 94 UK and overseas Society meetings, organised by The Society, to the declaration in October 2014. Awareness Reps work with us to promoteReview workThe in a specificsupport their role and enable networking field of goals was slightly lower than expected, 65%Society, membership, and access Rep-only with Reps based in other regions. but 60% of respondents support The grant schemes. High profile speakers Society’s goals and most respondents64% knew All Members can view a list of current Reps about specific activities. As a Rep you can apply for funds, as part via the membership directory, of the Departmental Seminar Scheme, to https://portal.physoc.org/Membership- Overall, the results of the survey are very support travel and accommodation costs Directory, and filtering by Committee on positive; members are supportive of the associated with attracting visiting speakers Society Representative. work being carried out by The Society and to departments. the Member-focused activities we deliver. Interested in finding out more? Read more We would like to extend our thanks to all the You are also able to nominate a student about the role of Reps at members who took the time to complete the for the Undergraduate Prize in Physiology, www.physoc.org/what-do-society- survey and we will continue to report specific recognising your institution’s best reps- do or get in touch with Jen Brammer, actions arising from this survey as they are BSc physiology research project or Membership Engagement Manager, at implemented. an outstanding MSc student who has [email protected] performed well throughout their degree. An executive summary will be made available Help us reach our aim of having a Rep for to all members on The Society website. We can provide support for open and every institution and organisation where AnyoneError! wishing No to text discuss of specifiedthe survey andstyle the in document.induction events, by either arranging for we have members! 2 results further, can contact Jen Brammer, Membership Engagement Manager, at [email protected]

13 News in depth

Belief, science and facts A March for Science in response to the recent US election

‘Science is science and facts are facts’ It was deeply satisfying to see so many appeared in a Donald Trump pre-election young children attending the rally. One 8th (2016) response to a science questionnaire grader spoke passionately and confidently distributed by Science Debate, a non-profit recited his essay titled, ‘Why I love Science’ organisation that urges scientific literacy and to surely the biggest tutorial group ever accountability from political candidates. Fast assembled! forward to Saturday, 22 April 2017 when your correspondents were enjoying a But we had one nagging worry, why in 2017, post-breakfast stroll around the Grant Park did we need a ‘March for Science’? Surely, we area of Chicago contemplating the have come a long way since Copernican ideas forthcoming board meeting of Experimental were deemed heretical and Galileo was Physiology set for that afternoon. It was then placed under house arrest? Surely, people that we joined a steady stream of people value scientists and see science as the with banners and signs making their way cornerstone of modern civilisation? towards the park for what was the pre- gathering of the March for Science. Soon we Well, apparently not. Increasingly, science is were joined by over 40,000 (some sources regarded by politicians as an inconvenience. Mike Tipton now state 60,000) people; in fact, numbers Worse, increasingly scientists are being University of Portsmouth, UK were so large that the police made media portrayed as alarmist, self-opinionated broadcasts to stop others attending ‘boffins’ who live in a fantasy world. They are funded by government yet, it is claimed by It was a diverse, buoyant crowd with some of some that they contribute too little to society. the best posters we had ever seen. The initial speeches were given from a stage erected in It struck us how easy it has become for the shadow of Trump Towers (a metaphor?). politicians and their publicity machines, to

Mike White University of Birmingham, UK

14 Physiology News / Summer 2017 / Issue 107 dismiss science as merely another form of lookalikes or Star Wars Stormtroopers at Nearly 500 years after Galileo, we have to personal opinion which can be sprinkled into the rally; they were all at the nearby fight once more for science. So, whenever TV ‘debates’ or denounced and occasionally Comic-Con event, where belief in time travel you get the chance and you catch someone supported in a short tweet, i.e. ‘science, bad!’ and teleportation would be easy to find. In using a device or marvelling at new or ‘really clean coal’. And how easily fact, our crowd looked remarkably normal technology remember to say ‘science did rigorously gathered, peer-reviewed evidence and diverse. that!’ can be dismissed as fake news because the implications of the evidence do not suit a Our collective memory of schoolboy science Time to boldly go... and engage? political viewpoint. In short, the virus that is may be rose tinted (we are after all two men ‘spin’ appears to have infected science. of a certain age) but it seemed back then that young people had a good idea where Ignorance of the is now science and technology could lead and what sufficiently widespread to avoid immediate it had contributed to society. Is it really the challenge to a preposterous statement. How case that many people now do not see this boring to organise a debate only to find that connection and are put off science by the all are in agreement, as the evidence is stereotypical portrayal of the mad scientist, incontrovertible! the white coat and the laboratory? ‘The science community is waking up to the But who is at fault here and why have we The rally in Chicago and others that took regressed? Is it the work of politicians, their place all around the world showed that there idea that we can no campaign teams and their marketing is a groundswell of opinion that supports strategists, for attacking what they see as an science. We as scientists must keep up the longer assume our inconvenient truth but one which they see is pressure on our politicians to understand and conveniently soft? Or are the scientists, support science and perhaps we all must do efforts and their value technologists and engineers at fault for more to educate and inform people about the assuming that everyone knows what they do work we do and its importance to society. To are automatically and how valuable it is to society, thereby ignore, disregard or belittle science is to producing that soft target. disregard a way of acquiring knowledge. An understood’ approach that has been developed and Many of the banners at the recent march in tested over centuries, which people have Chicago illustrated, with great originality and fought for and are fighting for again. humour, that perhaps the science community Science is a special method of findings things is waking up to the idea that we can no out; the bridge between belief and the truth. longer assume our efforts and their value are Importantly, science is also fun (some of the automatically understood. ‘Remember polio? time!). We are not the ‘geeks’ that are I don’t. Thank a scientist’ read one poster. portrayed in the media and we do have a life outside of science – some of us in rock bands! If we allow the media to continue to use (GI Distress, a group composed of scientists terms like ‘boffin’, when reporting any new including Kim Barrett, Editor-in-Chief of The discovery or technological advance, what Journal of Physiology, and Mark Frey, Senior picture does that conjure up in the minds of editor of Experimental Physiology, played a most people? We didn’t see any Dr Who gig at a pub in downtown Chicago).

15 News in depth

Stressed-out Britain? A report on our annual Theme and our survey

the topic meeting on The Neurobiology of Regional variaitions in Stress Lucy Donaldson Stress as part of the British Neuroscience Chair of Policy & Communications Association’s Festival of Neuroscience, and Committee, The Physiological Society virtual issues of our journals on stress.

As part of the annual theme, The Society’s Policy and Communications team took Are British people as stressed as we all think? another look at the stress of people across Everyone I talk to now mentions their the UK, in a broader group than just medical busyness, the speed of life, and the patients. We commissioned YouGov to expectation of immediate response or survey over 2000 people in January of this results. Has our stress really increased, and year. Respondents rated a shorter list of life are the same things causing stress now as in events according to how stressful they might the past? Are our parents correct in saying find them (YouGov survey, 2016). We life was simpler and less stressful ‘when they included some of the events from the SRRS were young’? as benchmarks, but also, after conversation with Professor of Health Kavita ‘Life’s most stressful events’, such as getting Vedhara of the University of Nottingham, married or moving house, are quoted time we included some potentially positive and again in the press. This list derives from events such as going on holiday or being the seminal work of Holmes & Rahe in 1967 successful at work. that resulted in the Social Readjustment Rating Scale (SRRS). In this work, 43 life Many of the key findings from the survey events previously correlated with the onset were not much of a surprise – going on of illness were rated by over 5000 medical holiday is the bottom of the list as we might patients. Marriage was given the standard expect, and just as Holmes and Rahe found. score of 500, and all other events were Similarly we would hope that success at work AverageAverage stress stress level level /10 /10 ranked in relation to it. The results form the or being promoted would be a reasonably basis for the ranked list of life’s stressful positive event, and (thankfully) it is close to Average stress level /10 events quoted today. It’s worth noting that the bottom of the list too. The events at the most, if not all items on this list are negative top of the list are hardly surprising either – events (Holmes & Rahe, 1967). death of a spouse or close relative was our There are many more conclusions to be benchmark for the most stressful event on drawn from these data. For example, there is

The stress response is a distinct combination the SRRS, but divorce has moved downFigure the 2: Regional evidencevariationsFigure in that 2: Regionalwomen variationsreport all thesein events of bodily responses that enable us to cope list relative to imprisonment or personalaverage stress as moreaverage stressful stress than men. Also, loss of your with challenges. Without this response, such illness. This may be because divorce now smartphone is more stressful for the younger challenges could be life threatening. This is carries less social approbation than in the generation (18–24) as is Brexit. There are the physiologists’ take. 1960s. Planning a wedding has become also differences in responses to these relatively less stressful (the wedding planner different events across the UK. We hope to The ranked list defines stress as the feelings is obviously worth it!). be able to examine the data in greater depth associated with a wide variety of situations, in a future issue of PN. rather than the physiological definition. For Obviously, updating a study from decades most people, stress is a condition or feeling ago afforded the opportunity to include This YouGov survey obviously has limitations experienced when a person perceives that some events pertinent to the 21st Century. – it’s not a ‘scientific’ study and isn’t really ‘demands exceed the personal and social Surprisingly, respondents said losing your directly comparable to the SRRS. It does, resources the individual is able to mobilise’ smart phone is only marginally less stressful however, give us food for thought on how (quote attributed to Richard S Lazarus). than the potential for terrorist threats, and our of life’s stressors may have more stressful than moving up the property changed. We included many of the negative Under our annual theme of ‘Making Sense of ladder. Contrary to the picture painted in the stressors in Holmes and Rahe’s list but also Stress,’ we are looking at stress in many media, Brexit is actually not very stressful for some potentially positive events. It is different ways. We have public events, such most people surveyed. important to remember that stress can as the lecture featuring Stafford Lightman, often be a positive experience. Hans Selye,

16 Physiology News / Summer 2017 / Issue 107 On a scale of 1 to 10, where 1 is ‘Not at all stressful’ and 10 is ‘Very stressful’, how stressful would you find the following situation?

Event Mean rank

Death of close spouse/partner, close relative or close friend 9.43 Going to jail 9.15 ‘Rather than fearing Having your home flooded or damaged by fire 8.89 stress, or always Being seriously ill 8.52 avoiding it, focus on Being fired from work 8.47 harnessing it by Separation, divorce or end of a long-term relationship 8.47 believing in a good

Experiencing identity theft 8.16 outcome and that you

Having unexpected money problems (e.g. due to car repairs, heating are in control’ breaks, etc.) 7.39

Starting a new job 6.54

Planning a wedding (i.e. the marriage/civil partnership ceremony) 6.51

Arrival of first child 6.06

Experiencing commute delays 5.94

Terrorist threats (i.e. the potential for them to happen rather than experiencing this personally) 5.84

Losing your smartphone 5.79

Moving to a bigger house 5.77 References

Brexit (the process of leaving the European Union) 4.23 Holmes TH, Rahe RH (1967). The Social Readjustment Rating Scale. Going on holiday 3.99 J Psychosom Res 11(2), 213-8.

Richard Lazarus (1922–2002). Professor of Getting a promotion or having success at work 3.78 Psychology, Emeritus, University of California, USA.

Selye H (1985). The of Stress. often considered to be the first person to Rather than fearing stress, or always avoiding Basal Facts 7(1), 3–11. demonstrate the existence of biological it, focus on harnessing it by believing in a stress, found that some stress can be good good outcome and that you are in control. YouGov survey. All figures, unless otherwise stated, for you, but it depends on how you respond In his 1985 paper ‘The Nature of Stress’ are from YouGov Plc. Total sample size was 2078 to the situation. (Selye, 1985), Hans Selye wrote about the . Fieldwork was undertaken between 22 importance of finding your own stress level and 28 December 2016. The survey was carried By motivating someone to tackle a challenge, to make sure that both the stress level and out online. The figures have been weighted and are stress can lead to feelings of satisfaction and the goal are really your own, and not imposed representative of all GB adults (aged 18+). accomplishment. It’s the spark that pushes us upon you by society. to do things we would normally not, and that extra encouragement is important, as In closing, it is worth reflecting on the without it, we would be complacent. Smaller summary provided by Selye himself, ‘Fight for amounts of positive stress – which Selye your highest attainable aim, but do not put referred to as ‘eustress’ – have been shown up resistance in vain.’ to enhance cognitive abilities and boost mental prowess. This is because it helps us focus on the task at hand. Some studies have even shown that it boosts memory – which is really helpful when writing a grant proposal, preparing for your viva or marking to a deadline!

17 News in depth

Introducing our MOOC in Physiology

are to enhance and extend at A-level and out of learning according to their needs Chrissy Stokes and equivalent, and to introduce concepts or timetable, and it meets the rising demand Head of Professional Development encountered in the first year of for digital learning. and Engagement, The Physiological undergraduate study (in physiology and Society related degrees), in order to support the Completing the MOOC will be helpful to all transition to university. students whose post-16 qualifications include physiology components. It will also Three core topics, common to UK benefit those looking for extension learning Sarah Hall examination boards (for A-level Biology or before university, and may help to inform Chair of Education and Outreach equivalent), will be covered in the MOOC; those making difficult degree choices. Whilst Committee, The Physiological Society these are the cardiovascular system, the we have identified students making the respiratory system and the . transition to university as the target There is growing concern about students’ audience, we are aware that the general lack of preparation for university, especially demographic of MOOC learners extends Massive Open Online Courses (MOOCs) are with regards to their mathematical beyond this – most tend to fall within the university-led, distance-learning courses understanding. To address this, the MOOC age range of 25–40 and to possess one or that are freely available online. The will include activities on data handling, more degrees already – and this has been a introduction of MOOCs around a decade ago particularly physiological measurements. consideration during the development of our generated considerable excitement and There will also be information about careers MOOC. Although the broader public are expectation, with free access to everyone, in and from physiology. School teachers and unlikely to include the next Nobel Prize unlimited participation and low running costs members of The Society’s Education and winner, they may be their relative, or a promising to extend a university’s Outreach Committee have the opportunity politician, and they will almost certainly be educational activities beyond its bricks and to review all the content produced by the voting. The MOOC will therefore have a mortar. However, the excitement soon faded University of Liverpool. broader impact, raising the profile of amidst reports of low completion rates and physiology and improving understanding of, copyright issues. Academics have now MOOCs are an attractive platform for both and appreciation for, our discipline. reached a more balanced view of the role of the learner and provider: they are freely MOOCs in the education arena. accessible to anyone with an internet Enrolment for the physiology MOOC will connection, content can be updated as open in the summer, and the course trailer The Education and Outreach Committee necessary, and it facilitates the interaction of also provides an insight into the content. We watched these developments unfold, guided students and physiologists (through hope that Members will be active in by the expertise of one of its members, moderated discussion sessions), it provides a encouraging their local schools, and other Professor Neil Morris, who now holds the comfortable insight into university learning interested individuals, to participate, and we Chair of Innovation and Change at the (demystifying the institution that may seem look forward to reporting back on the University of Leeds. After considerable daunting to 16-year-olds), users can dip in success of the course later this year. research and reflection, we began a bumpy journey to develop a MOOC that would help to raise the profile of physiology, and support the progression of students into physiology and related disciplines. Fast forward to 2017, and we are pleased to announce The Society’s MOOC in physiology, entitled ‘Physiology: The Science of Life’, will run for the first time this autumn. It has been produced in collaboration with the University of Liverpool, our content provider, and is hosted by FutureLearn, one of the leading MOOC platforms.

The target demographic for our MOOC is A-level (or equivalent) students who are Terry Gleave teaching respiratory considering studying physiology, life science physiology as part of the MOOC or medicine. The primary aims of the MOOC

18 Physiology News / Summer 2017 / Issue 107 Reddit ‘Ask me Anything’ (AMA) with Kim Barrett We ask The Journal of Physiology’s Editor-in-Chief about her experience

Kim Barrett

Reddit is a massively popular social news and Were you surprised by the amount of also a good opportunity to highlight The discussion website with over 234 million engagement? Journal of Physiology special issue on the members that has over eight billion page microbiome [J Physiol 595(2), 415–598], views per month. The ‘subreddit’ r/Science This really blew me away. When I logged on to which was published in the same week. (also known as the The New Reddit Journal of the AMA I was amazed to find more than 1000 Science) has over 16 million subscribers – that questions there already, with more coming in Would you do an AMA on Reddit again? means over 16 million people interested in as the session began. I started out at the top of science! Reddit is a great way to engage with the list, but soon realised I could not possibly I would gladly do this again. Perhaps the only the online community and Ask Me Anything answer everything. After a while I started limitation is that with the number of (AMA) sessions allow experts to spread their cherry-picking a bit to select the questions questions and the time allotted, it was not knowledge through an informal Q&A. that were either the most straightforward to possible to engage in lengthy conversations answer, or the most interesting to me. with individuals. We asked Kim Barrett, Distinguished Professor of Medicine at UC San Diego and Was there a big difference between Would you recommend that other Editor-in-Chief of The Journal of Physiology, engagement with the public and scientists engage with Reddit? about her experience doing an AMA about her scientists? Were the questions vastly research on Reddit. different? I think it’s really important that we as scientists make efforts to provide our expertise to the Kim’s AMA proved to be largely popular with The majority of questions were thoughtful public and explain our areas of research in ways over 1500 ‘upvotes’ (equivalent to likes on and appropriate no matter who was asking that are understandable to all. This is Facebook) and over 200 comments and them. It was clear that there were quite a few particularly urgent when research and research questions. The co-creater of Reddit, Alexis scientists and doctors engaged, but also funding seems to be under attack. On both Ohanian, also chipped in on Twitter, thanking members of the public. sides of the Atlantic, we need the public on our Kim for her contribution to the science side to convince policymakers that research is subreddit. Were there any surprising questions? a sound investment for public funds.

Reddit is a great way to engage with There were a number of questions that What are your top tips for other thousands of people about your research – addressed quite personal and specific health scientists or academics who want to do and it’s free! All it takes is a minimal amount issues. I guess I should not have been an AMA? of planning and a few hours of your time. surprised, but it also was certainly not the venue to offer heath recommendations. There It is important to define a topic that is was also a fascinating question from an sufficiently broad and topical to attract Have you ever used Reddit before? Did individual who wanted to know whether his interest, and to address your answers to an you find it easy to use and to schedule childhood habit of ingesting washing up liquid educated lay audience. I was a bit intimidated the AMA? bubbles would have altered his microbiome. at the beginning but it is important to I’ve never heard of kids doing that! remember that you are not on stage and I had hardly even heard of Reddit before my there is nothing to prevent you looking up a AMA. The conventions, acronyms and What are the advantages of engaging few facts before committing to an answer. language were a bit intimidating at first. It with the public on Reddit? The most important piece of advice is to just was easy to navigate the scheduling but I jump in. It’s only a two-hour commitment and didn’t receive much in the way of confirmation This was a low risk, efficient way of engaging there is a lot of flexibility in scheduling it at a and feedback, leaving me a bit uncertain up till with a lot of different people from all over the time that suits you. I was so intrigued by the the day whether it was really going to happen, world. It is a very easy way to highlight an questions that I actually went back at or if I had messed up somehow. area and get your expertise out there. It was lunchtime and answered a few more!

19 Meetings & events

2017 Forthcoming events 12 July 1-5 August 14-15 Sept. 8 Dec. Annual General Meeting and IUPS 2017 – The Rhythms of Life Mitochondria: Form and Function H3 Symposium: Sensory President’s Lecture RIOCENTRO Exhibition & Hodgkin Huxley House, Transduction in Insects Wellcome Collection, Convention Centre London, UK Hodgkin Huxley House, London, UK Rio de Janeiro, Brazil London, UK www.physoc.org/ www.physoc.org/agm-2017 www.physoc.org/iups2017/ mitochondriaformandfunction/ www.physoc.org/ sensorytransductionininsects/

We planned to increase positive attitudes by Meeting Preview enhancing practical education, encouraging student-led investigation and enquiry, and supporting local teachers. The project put IUPS: the Two-way students in charge of their own learning and Physiology Street and lab space while being facilitated by a ‘Scientist in Residence’ such as myself. Just like adult the Mutual Benefits of scientists, young people in the lab proposed Volunteering Expertise their own questions based on their world and, with support from a Scientist in Residence, worked through IUPS 2017 experiments to determine their own answers. Rio, Brazil This was in contrast to traditional talk and Anisha with students in Ghana chalk teaching methods usually employed in rural schools, with many teachers believing that ‘doing’ science required specialist labs You can read a fuller account of my Anisha Tailor and equipment that only the richest schools experience in PN 101, Winter 2015, pages have access to. 14–15, or, if you are heading to Rio this Outreach Officer, summer for IUPS, you can join me in the The Physiological Society Our stock cupboard was the local markets and symposium ‘The Two-way Physiology Street our recycling. My experience allowed me to and the Mutual Benefits of Volunteering witness first-hand a change in student Expertise’. Joined by physiologists discussing In 2015, I took a six-month sabbatical from attitudes towards science in just 6 months their volunteer work in Zimbabwe and Nigeria, my role as Outreach Officer at The of a student-led approach. It has not only we will be discussing the benefits of Physiological Society to set up the pilot given me insight into the struggles of volunteering, the discrepancies in the world education project, Lab_13 Ghana. The project teaching science with limited resources, but between areas with plentiful resources and aimed to establish a ‘proof of concept’ for a an understanding of what local teachers want those who are resource poor, and the new model of science education in resource- to gain from internationals making visits to importance of partnerships. constrained environments. their school.

20 Physiology News / Summer 2017 / Issue 107 My attendance at the event was facilitated by and the impact on (Andrea Meeting Notes the support of The Physiological Society, who Danese – King’s College London, UK) provided me with a travel grant in order to British Neuroscience attend. I cannot thank them enough for their • See what you hear – how the brain forms support, as I found the conference to be a representation across the senses (Uta Association 2017 Festival extremely beneficial, both in terms of Noppeney – University of Birmingham, UK) personal interest and the gain of experience. of Neuroscience The highlights of the festival for me • APOE4 from man to mouse (Sarah King – personally were the daily poster sessions, University of Sussex, UK) 10–13 April 2017, some of the talks that were not related to my ICC Birmingham, UK research but of a great interest to me, and • Structural and cellular studies to elucidate The Physiological Society’s own symposia on the mechanisms of APOE isoform action the theme of The Neurobiology of Stress. and provide targets for therapy (Louise Serpell - University of Sussex, UK) Molly O’Reilly The daily poster sessions were a really exciting part of the conference – the poster As you can see, some of my favourite talks University of Sussex, UK hall was lively and buzzing every day. The were from researchers based at my own poster sessions were grouped in terms of institution. It can be so easy to immerse their subject area, and I attended each day. yourself in your own research and lose sight I am a third-year PhD student at the The enthusiasm in the room was inspiring, and of what other researchers within your University of Sussex, and this past April I everyone was so inquisitive. During my own institution are working on, so it was really was given the opportunity to attend the poster session, I had a great deal of interest enlightening to get a glimpse into this. There British Neuroscience Association (BNA) and a constant audience, alongside lots of was a great representation of different festival of Neuroscience, held in Birmingham. good questions and useful suggestions. institutions at the festival and a really broad My research focuses on preventing the I have already used some of the suggested set of delegates. hearing loss associated with clinical drug ideas in my research back in the laboratory. treatments, which is rather a niche area. I highly recommend attending these types Lastly, the topic of neurobiology of stress The conference was therefore a fantastic of events. really ignites my interest, so I was pleased to opportunity to network amongst the broader be able to explore this in such a neuroscience community. It also provided a The talks were also very good – there was comprehensive manner through The Society’s chance to broadcast my research, as I was such a diverse range of topics and symposia. The symposia were led in such a selected to present a poster and also give a presentation styles. As an example, some of way that researchers without prior knowledge short talk during the rapid-fire poster my favourite talks included: could engage. Overall, the conference was a session. As I had previously not given a fantastic experience and I cannot commend talk to such a large audience, it was an • The hidden wounds of childhood trauma: The Physiological Society enough for their invaluable experience. of early stress role in my ability to attend.

aim of enhancing laboratory skills for identify issues and help in experimental Meeting Notes researchers. One such workshop was the troubleshooting, and even exchange ideas for ‘Introduction to Molecular Biology Techniques, future experimental work. The staff, Transfection and Functional Studies’. As a especially Caroline Pellet-Many, were Our Workshop: first–year PhD student in the School of exceptionally friendly and cooperative, and Introduction to Molecular Pharmacy in Reading University, I found this helped us design protocols which we can workshop was a great opportunity to enhance apply in our own research. Additionally, during Biology Techniques, my laboratory skills and learn new laboratory the workshop, we were given an interesting techniques which are valuable for a career as tour around the old hospital, where we were Transfection and a research physiologist. shown the mosaics which cover parts of Functional Studies the teaching labs that used to be the The workshop was divided into two sections. children’s ward. 25–28 April 2017, The first entailed an introduction to basic essential techniques used in molecular biology, Overall, attending this workshop was an University College London, such as RNA extraction, reverse transcription exceptional opportunity to learn and become London, UK and PCR. The second section focused on confident in techniques which are widely used techniques used for cell transfection and in research. It was enlightening to learn about techniques to investigate protein expression other researchers’ work, and it fired my and functionality, such as the widely used enthusiasm for my own research. I am Eleni Kaisis SDS-PAGE and Western blotting. grateful to the Alzheimer’s Association for funding my attendance, and to The University of Reading, UK The workshop provided a nice balance Physiological Society for providing me with between background theory and laboratory the opportunity to attend this extremely practicals. During the dinner provided by helpful and inspiring workshop. Following the success of previous years, this The Society, and the numerous coffee and tea year The Physiological Society has again breaks, we all had the opportunity to network sponsored a number of workshops with the and discuss each other’s research work,

21 Following the meeting, the organisers have In Sheila Amici-Dargan’s (Cardiff) talk Meeting Notes received excellent feedback including reports ‘Platforms with Potential’, her team invited of new collaborations forming and new students to use Learnium (another social H3 Symposium: approaches being considered; we hope to also learning platform) to enhance their report on the development of these in future understanding of human pathophysiology. Practical Innovations in issues of Physiology News. In the context Their research showed that over half of the of this feedback, the organisers considered students surveyed said they used the system, the Life Sciences the event to be very successful (and co- while 54% stated they felt it was either organiser, Nick Freestone, shared his thoughts useful or very useful. in a recent blog) but we have encouraged other attendees to share their perspective. This raises ethical questions about benefit On this page and the next we have pieces sharing and revenues when universities from Dr Harry Witchel, questioning interact with commercial organisations the interplay between universities and providing a nominally free service. Research commercial IT providers, and from one of our is expected to provide shared benefits undergraduates who contributed with a talk to participants, communities providing summarising his experiences of completing a ‘biological’ material and future generations, as final year project on public engagement. well as to the researchers, their universities and profit-making organisations. For example, when geneticists research a family with a rare genetic disease, individual research participants may have a right to share the benefits/profits of the intellectual property. Likewise, when traditional plant knowledge of an indigenous people is developed into a potential treatment by a company, we expect the indigenous people to benefit equitably. However, not all benefits are revenue 25–28 April 2017, streams, and in many cases there are practical University College London, difficulties in revenue sharing with research London, UK participants, even in genetics research.

How does this play out in ethical approval for pedagogic research with commercial IT Chrissy Stokes platform providers? Commercial enterprises Head of Professional Development benefit from voluntarily engaged university- driven teaching research because of the & Engagement, The Physiological publicity for the commercial platform and the Society database of use statistics they gain. Yet, as shown in the H3 symposium, these platforms are routinely used in educational research, ‘Practical Innovations in the Life Sciences’ and it is not standard ethical practise for was an H3 symposium organised by the universities to charge the commercial Education and Teaching Theme Leads, Sheila IT platform providers for access to their Amici-Dargan, Nick Freestone and Derek Harry Witchel students. Quite the opposite, the commercial Scott. The two-day workshop was put Senior Lecturer in Physiology, social learning platform providers often together to facilitate the sharing of new ideas Brighton and Sussex Medical School, UK can charge money for user-access to those and best practice in practical and classroom platforms. The argument is that this is not teaching, as well as engagement with the exploitation because the student end-users public. The audience included educational benefit indirectly via later improvements in practitioners and developers, technicians and Future issue: their career prospects. undergraduate students. ethics, governance and Reversing these institutional arrangements Day one focussed on teaching practical commercial enterprises that benefit large platform providers is ‘one of science, with talks showcasing a variety of in research on social the major tasks now facing a critical political tried and tested methods to improve student economy of culture and communications’ engagement, skill and understanding. Day learning platforms [Murdock G (2011). Political economies as two began with a plenary session on the use moral economies: commodities, gifts, and of technology in learning, and was followed public goods. In: Wasko J, Murdock G, Sousa H by sessions on alternative approaches to At the ‘Practical Innovations in Life Science (Eds), The Handbook of Political Economy of classroom teaching and public engagement. Education’ H3 symposium, physiologists Communications. (London: Wiley-Blackwell), (and other life scientists) showed how they pp. 11–40].Thus, in the current climate, when Amongst the talks there was also a successfully incorporate social learning senior managers request under-resourced structured discussion looking at common platforms into their didactic service provision education researchers to demand payments obstacles in teaching practical physiology and pedagogic research. Many of these IT from commercial social learning platform and opportunities to ‘stretch the able’, with platforms are externally provided, commercial providers in order to provide additional revenue attendees providing invaluable feedback systems, including the ubiquitous Quizlet to the university, it may be less related to regarding potential opportunities for The [as highlighted by Louise Robinson’s (Derby) current best practice in ethics or governance, Society to provide support in these areas. talk on ‘Gamification in HE Teaching’]. and more related to wishful thinking.

22 Physiology News / Summer 2017 / Issue 107 From the Archives: reports by the Meetings Secretary JS Gillespie of the Leeds and Cambridge meetings of 1967

Transcribed by Roger Thomas

Leeds Meeting, Cambridge Meeting 14-15 April 1967 7 July 1967

At the invitation of A Hemingway, a meeting At the invitation of BHC Matthews a of The Society was held in the Department meeting of the Society was held in the (L–R) Elodie Cox and Patrick Evans of Physiology, Leeds University, on 14 and Physiological Laboratory, Cambridge on 20 15 April 1967. Beginning at May 1967, beginning at 10.30 am. 2 pm on Friday, five papers were heard before tea, which was followed by a very full Although this meeting had the almost Patrick Evans programme of demonstrations, including expected pleasure of an unusual several of the risky, live sort, all of which Demonstration by GS Brindley who, on this University of Bristol, UK behaved splendidly. Members and guests occasion, played a recorder at both ends and were then transported to Bodington Hall for showed a power-assisted bassoon, the sherry, dinner, an informal resumption of the meeting did have a number of unusual An undergraduate meeting in the bar until 11 pm and finally a features. Because of the rising number of good night’s rest. After dinner, E Neil, in Communications, the meeting had been perspective on speaking proposing The Society’s thanks to its hosts, divided and 18 Communications were given mentioned that this would be the last in one theatre, with BHC Matthews in the at a Society symposium occasion on which A Hemingway would be Chair, while 16 Communications were given the Chairman at Leeds. He remembered with in a second theatre with WAH Rushton and affection the time spent working in EB Verney as Chairmen. Although one was I became aware of the workshop through Professor Hemingway’s department, and withdrawn, there were three extra my third-year supervisor, who advised us to paid tribute to his many sterling qualities demonstrations bringing the number to 11; give a talk about our final year neuroscience including that of fitness through regular the Chairman modestly regretting that there dissertation project. It was a public exercise which he, E Neil, in his own fashion, were not more to an audience which is engagement project, which was a new type constantly emulated. RJS McDowall also annually astonished by the efforts of of project trialled for the first time this year. spoke appreciatively of A Hemingway, departments which, in and out of term, can Together with my project partner, Elodie Cox, whom he had both taught and later had on like Cambridge, demonstrate so well year we created a video to explain our designated his staff at King’s. In reply, A Hemingway after year. topic, which was memory engram cells, welcomed Members and guests, thanked and presented it to a non-scientific public the members of his staff for their work in Later, after sherry generously given by the audience. We thought it would be of interest preparing for the meeting and hoped that University, Members and their guests had to share our experience. when next The Society visited Leeds it the unusual priviledge of dining, in term would be in a new department, part of the time, in the Hall of Pembroke College – Although I was initially quite nervous to be ambitious and exciting development of a particular triumph for J Hickson who had attending a workshop alongside university the University. persuaded the undergraduates to dine early staff, it soon became clear that it would be and the Fellows to dine elsewhere. Here a very valuable experience. There were a lot On Saturday, the remaining part of the there were many distinguished foreign of ideas to be shared and it was great to see programme was taken in Bodington Hall, Members and guests including R Stampfli, how absorbed and interested everyone was where Members, deeply ensconced in Y Zotterman and SA Krolenko; with HH Dale in each other’s presentations. The morning armchairs, remained remarkably vigorous, at the high table the dinner became a presentations were focused on the use of though sometimes invisible, in discussion. special occasion. technology in university, so as a student I felt Under the successive chairmanships of very relevant to the discussions. The second A Hemingway, WJ O’Connor and After dinner, Y Zotterman, in a typically session saw more talks on the theme of RJ Linden, the remaining 15 papers were vigorous speech, thanked the Chairman and public engagement. It gave me an insight to given and the meeting ended at 3.30 pm his colleagues. BHC Matthews in reply a completely different side of university and with tea. Demonstration 5 and welcomed The Society’s guests, especially it was encouraging to see the attendees were Communication 3 were withdrawn. the Master of Pembroke College. enthusiastic and committed to benefitting our learning. Friday 14 April – Saturday 15 April Everyone present drank to the health of Signed: Bryan Matthews HH Dale who in return entertained them by In the future, a combined attendance of accounts of earlier and more robust university staff and students alike could be Tea 100, Coffee 91 meetings when Chairmen could tremble with very beneficial to both parties – after all, us Dinner 107, Lunch 91 rage and irritation. On this amiable note this students will be the first-hand receivers of Tea 73 very agreeable meeting ended. many of the ideas that were discussed. Signed: GL Brown 7 July 1967

23 Features

The open science movement Revolution is underway

‘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, and fundamental shifts on the horizon in both Philosophical Transactions, was published the ways we communicate (i.e. preprints) by the Royal Society in 1665. At last count and carry out science (i.e. open data and there were some 11,365 science journals open notebook science). Featuring in the spanning over 234 disciplines by 2015, and next issue of Physiology News, the second yet the primary model of scientific publishing half of the series (Opening Up Science remained largely unchanged throughout Education by Vivien Rolfe) will illustrate how the centuries. open education has democratised access to knowledge and fostered engaging and As a fresh-faced, naïve PhD student, I recall creative approaches to learning and teaching. the horror I felt upon learning that my hard Keith Siew work would be at the mercy of a veiled, Open access – ‘tear down this wall’ political peer-review process, that I’d be left University of Cambridge, UK with little option but to sign away my rights In 1991, Sir Tim Berners-Lee gifted us the to publishers, and too often forced to choose World Wide Web, forever changing the way between burning a hole in my wallet or we would access information. Fast-forward a forgoing access to a potentially critical paper! mere quarter of a century later, and mobile- broadband networks now reach an estimated The open science movement offers an 84% of the global population and almost half alternative to this unjust system. In its purest of the planet engages in regular internet use. form, the movement advocates for making This ultimately resulted in giants like JSTOR, scientific research and its dissemination PubMed and Google Scholar displacing an entirely transparent process, freely libraries as bastions of knowledge, and has accessible to all levels of society. The aim ushered in an era of private, freely available, of this two-part series is to present an internet-based repository/database- overview of the various incarnations of searching from the comfort of one’s office open science and recent paradigm shifts. or home. In particular, I address some of the more radical elements of the movement, existing During the rapid transition from paper open science opportunities and the reasons to PDF, publishers took advantage of behind life scientists’ relatively slow adoption opportunities to boost profits (Fig. 1), and of open science. This first installment details continued the practice of hiking subscription the ongoing struggle for open access, the fees at rates far in excess of annual inflation growing angst towards closed (Dingley, 2006).

24 Physiology News / Summer 2017 / Issue 107 1,500 50

1,200 40

900 30 ‘As of April 2017, more than 860 research and 600 20 funding organisations Profit margin (%) margin Profit (%) margin Profit worldwide have Operating profits (million US$) profits Operating 300 10 adopted open access mandates’ 0 0 1990 1995 2000 2005 2010 2015

+ Operating profits o Profit margin

Figure 1. Profits from the scientific, technical & medical (STM) division of Reed-Elsevier (renamed RELX Group in 2015). Larivière V, Haustein S, Mongeon P (2015). The oligopoly of academic publishers in the digital era. PLOS ONE 10(6), e0127502. [DOI: 10.1371/ journal.pone.0127502]. © 2015 Larivière et al. and is licensed under CC BY 4.0.

In the face of increasing soft copy demand call to action, setting forth the principles of In spite of great leaps forward in open and dwindling print production costs they open access and its definition, boldly stating: access, little has been done that addresses chose to erect electronic paywalls and enforce ‘By ‘open access’ to this literature, we mean works that predate, or are unaffected by, copyright transfers, a crude yet effective it’s free availability on the public internet, open access mandates. As a result, this transplant of their existing business model. permitting any users to read, download, half-measure has been rejected by those It was this perceived blatant profiteering, copy, distribute, print, search, or link to the unwilling to settle for anything less than the exemplified by the continued imposition of full texts of these articles, crawl them for total liberation of scientific knowledge. The nonsensical ‘traditional print’ service charges indexing, pass them as data to software, most notable of these crusaders was the for online materials (e.g. colour figures, or use them for any other lawful purpose, focus of an award-winning documentary, page counts and supplements), and ongoing without financial, legal, or technical barriers The Internet’s Own Boy: The Story of Aaron disenfranchisement of authors from their other than those inseparable from gaining Swartz (Knappenberger, 2014). In 2001, the work that fueled growing frustrations and a access to the internet itself.’ fourteen-year-old Aaron developed code for hunger for alternatives. the RSS feed and by fifteen was The legacy of these declarations was the collaborating with Sir Tim Berners-Lee to A change in winds occurred in 1996 when the ‘Open Access Mandate’, a policy which enhance internet functionality. He also co- editor of the Journal of Clinical Investigation requires researchers to make their articles founded Reddit and worked on the team whimsically declared: ‘The vexing issue of the open access by self-archiving the author’s that launched Creative Commons – the easy day is how to appropriately charge users for final peer-reviewed (and often non-typeset) to use copyright licenses that empowers this electronic access. The nonprofit nature version in a freely accessible repository, so authors and has become the mainstay of of the JCI allows consideration of a truly called ‘Green OA’ (usually after an embargo open access publishing. Surprisingly, it was novel solution—not to charge anyone at all!’ period), or by publishing them in an open his highly influentialGuerilla Open Access Early adopters of this refreshing ‘open access’ access journal, also known as ‘Gold OA’. As Manifesto and the events that followed approach were perfectly positioned to reap of April 2017, open access mandates had which would inspire the movement. Published the benefits of increased exposure from been adopted by more than 860 research in 2008, the manifesto called on academics new, government-run, digital repositories and funding organisations worldwide. to revolt against the system by downloading such as PubMed Central, and would later go This has been coupled with an explosive copies of paywall-protected articles to on to inspire pioneers of wholly open access proliferation of open access scholarly journals publish online for the whole world to see publishing models like Biomed Central and across all disciplines, which now total over (Swartz, 2008). Two years later, while a PLOS (Public Library of Science). 9,427 from 129 countries, with Gold OA research fellow at Harvard, Aaron would representing a significant proportion of new singlehandedly download over 4 million The culmination of the Budapest Open life science articles (Fig. 2). Governments documents from JSTOR using MIT’s network. Access Initiative, Bethesda Statement have also implemented mandates, including His intention was to publish the entire on Open Access Publishing and the infamous UK REF (Research Excellence JSTOR repository online and make it freely Declaration on Open Access to Knowledge Framework) implementing an open access accessible, but he was arrested in 2011 in the Sciences and Humanities from 2002 policy last year and the Council of the before finishing. Despite JSTOR reaching to 2003 proved most influential in the open European Union calling for immediate open a settlement in the civil case with Swartz access movement. Together, they made a access as the default by 2020 (Enserink, 2016). wherein he surrendered the downloaded data,

25 Percentage

0.000 4.533

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0

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Figure 3. Proportion of life science peer reviews Figure 2. Life science publications made available globally through gold open access that were published (EU only). [http://ec.europa. journals (not including hybrid journals). [http://ec.europa.eu/research/openscience] eu/research/openscience] © European Union, © European Union, 1995–2017 1995–2017

Federal prosecutors sought to make an According to Science Magazine, Sci-Hub is Open review – ‘out of the darkness’ example of this ‘hacktivist’ and brought 13 either ‘… an awe-inspiring act of altruism felony charges against him to the tune of or a massive criminal enterprise, depending Scholarly communication forms the bedrock 50 years in prison and $1 million in fines. on whom you ask.’ Elsevier would certainly of science and is the currency in which Tragically, on 11 January 2013, afflicted with place it in the latter category, with Alexandra academics trade. Its integrity and quality was depression and under enormous pressure residing in Russia to evade lawsuits and to be safeguarded by editorial oversight and from the trial, Aaron Swartz committed extradition, and Sci-Hub safeguarding itself peer review; a process instituted by the Royal suicide at the age of 26. against shut-down attempts by taking refuge Society of Edinburgh when Medical Essays on the and replacing compromised and became the first formally In the aftermath, Alexandra Elbakyan – a domain names as quickly as a decapitated peer-reviewed publication in 1731. Applied young neuroscience graduate student and hydra sprouting new heads. Despite some irregularly and in numerous variations, it computer programmer – was hailed as success with heavy-handed litigious efforts would not be until the mid-20th century that the spiritual successor to Aaron Swartz. in the past, there is now great anxiety the practice was to become commonplace, Launched in September 2011, her Sci-Hub among publishers that refusal to adapt may finally transmuting into the externally Project became the first pirate website in leave them on the losing side of this culture recruited, anonymous, peer-review process the world to provide free access to more war. For example, over half of all materials we are familiar with today. Now, amidst than 62 million research papers. It works hosted on the popular scholarly networking crises in both study replication and academic by first searching for an existing copy of site ResearchGate were uploaded in direct publishing, we must question if our current the paper in question on LibGen (Library defiance of publishers’ copyright, while nearly system of peer review has become unfit for Genesis), a repository of pirated literary 88% of surveyed Science Magazine readers purpose and is in need of radical redress. materials (where one can also find a myriad see nothing wrong with downloading pirated of academic textbooks). If it cannot deliver a papers with three in five having actually used Much of the criticism is levied against copy, Sci-Hub will bypass publishers’ paywalls Sci-Hub in the past (Travis, 2016). Even masked peer review centres on the potential and download a copy to LibGen by running those averse to dabbling in the morally grey abuses of power by editors and reviewers through multiple institutional access systems can now comfortably circumvent paywalls shielded by anonymity. While the vast and utilising login credentials anonymously using a free, fast web-browser extension majority are honourable, authors must trust donated by academics sympathetic to the called Unpaywall, which trawls 5,300+ public that reviewers will not suppress dissent cause. By February 2016, Sci-Hub was repositories to retrieve legal copies of papers. against mainstream theories, exploit ‘insider averaging 200,000 downloads per day from information’ to gain advantage, plagiarise all corners of the globe. Surprisingly, some This changing landscape leaves us with a or even deliberately delay publications from of the most intense use was concentrated question: in a world where total open access competing groups with unnecessary revisions. in resource-rich European and American seems inevitable (by either legitimate or Universities, suggesting that aside from nefarious means), can the centuries-old Although not a new idea, open peer review genuine access issues, the convenience of a scientist–publisher relationship survive seeks to solve these issues by introducing fail-proof centralised is just and do traditional publishers belong in the complete transparency to the process. too great a temptation to ignore. future of online community-driven science In this system, reviewers’ comments communication? and correspondence with editors and

26 Physiology News / Summer 2017 / Issue 107 arxiv q-bio F1000Research bioRxiv preprints.org Nature Precedings PeerJ Preprints The Winnower Wellcome Open Research

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Figure 4. The number of life science articles submitted to preprint servers and open publishing platforms prior to peer review. Created using data from the PrePubMed search engine. Created by Jordan Anaya ©, and is licensed under CC BY 4.0.

authors is published alongside their names in open peer review models, such as that make moves to create their own custom transparency documents. The advantages spearheaded by F1000Research. This solutions. So far the of this approach are many, as it not only unorthodox process typically involves a and Gates Foundation have contracted deters professional misconduct but also quick sanity check by in-house editors F1000Research to manage their own open credits reviewers for their work (via before articles are published online (often publishing ventures, namely Wellcome Open initiatives like Publons), allays authors’ within days of submission), then later Research and Gates Open Research, with misgivings, and educates the reader on arranging for invited open peer review the European Commission rumoured to soon the perceived weaknesses of the study post-publication to Pubmed-indexed follow suit with its own platform. However, and the steps taken to strengthen key articles. In acknowledgement of the value the two systems need not be mutually conclusions. In the past, publishers have of this approach, NCBI developed PubMed exclusive, and life scientists can borrow a been slow to implement this with critics Commons to introduce an additional level tried and tested middle-ground solution fearing that reviewer self-censorship would of peer review post-publication to PubMed from their cousins in the physical sciences diminish peer review rigor. However, the articles. Here, indexed authors can openly – preprints! data does not support this assertion with question or share information on the no negative impact on review quality found work of their peers, with responses publicly Since 1991 physicists have been depositing between open versus closed peer review in displayed under the relevant abstract for electronic, open access, preprint manuscripts randomised controlled trials. discussion. on the online repository arXiv, whereas the vast majority of life scientists have either In parallel with the normalisation of open Proponents of post-publication peer review never heard of preprint servers or don’t fully access practices, open peer review has argue that its greatest strength is the understand them. In physics, astronomy, experienced a resurgence in popularity. increased speed of access to information. mathematics and computer science it is Recently, several journals have introduced The median time from submission to now standard practice that completed editorial transparency policies either publication has hovered at 4–5 months manuscripts be deposited on public preprint mandating or giving authors the option over the past 30 years, although the servers prior to, or with simultaneous to have their pre-publication peer review traditional model has also meant that submission to, scholarly journals. This has proceedings published (although not always over half of all authors have had to endure been accepted as a means for authors to with reviewers’ identities disclosed). This has a wait of 1–5 years for a paper to be rapidly disseminate important findings to led to a doubling in the number of European published during their careers (Powell, boost the visibility and citation impact of life science peer reviews published (with 2016). Notwithstanding the delay in their work (e.g. astrophysics papers with reviewers named) in 2016 compared to time to publication, there is still a general a preprint counterpart are cited twice as 2014, although the percentage is still low at reluctance to replace pre-publication with much as non-preprinted publications), whilst ~2% of all peer reviews (Fig. 3). solely post-publication review models for also establishing priority for discoveries, fear it may reduce the overall quality of documenting evidence of ongoing projects Funding bodies have also shown keen papers. Though attitudes may soon change for career progression, and gathering early interest in moving towards more transparent as funders recognise the potential benefits of feedback to improve their papers for later systems, paying close attention to the providing their fellows with rapid, transparent formal peer review publication. emergence of novel post-publication publishing routes, and begin to gradually

27 The first life science preprint server Nature This solution would bring us closer to For a growing number of journals wishing Precedings was launched in 2007, although the reality of a ‘one-stop shop’ for all life to support reproducibility, it is a condition with seemingly little appetite they ceased science preprints that will both greatly of publication that raw data be hosted accepting new submissions after a 5-year accelerate research and establish preprints alongside the paper or deposited in a citable period. Shortly after, a renewed interest as the currency for determining priority of public repository. Demand for the raw in open science led to exponential growth a discovery. And for those who are still not data underlying a paper’s figures is not the in preprint numbers and creation of convinced by this, I’d highly recommend only driver for the burgeoning creation of several servers catering to the life science reading the ‘Ten simple rules to consider repositories, with open citable platforms community. The lion’s share of these new regarding preprint submission’ for more on like Figshare catering for unpublished and preprints now go to bioRxiv – a platform this topic (Bourne et al., 2017). published research outputs in any file launched by Cold Spring Harbor Laboratory format from posters and presentations to in 2013 modelled on the success of arXiv Open research – ‘what’s mine is yours datasets and code. This taps into a wealth (Fig. 4). It now hosts over 10,000 preprints and what’s yours is mine’ of information that would otherwise which are searchable on prepubmed.org remain locked away in hard-drives and and recently received a cash injection from Today we live in a world where separating notebooks, giving new life to miniature Facebook co-founder Mark Zuckerberg and fact from fiction has become a non-trivial studies, negative results and optimisation his wife, Priscilla Chan, to develop task. Our senses are bombarded daily by experiments which may be critical to an open-source platform and web-friendly ‘alternative facts’, experts find themselves replicating crucial results. article formats. mired in false equivalencies, and political talking heads present opinions, feelings and While the move to open data has been Nonetheless, many still fear that preprints anecdotal evidence on an equal footing with generally welcomed as positive, there is could lead to getting scooped by that which is empirically true. Be it climate mounting tension between speeding access competitors, missing out on credit for ideas change denial, anti-vaxxers or the war on to data and protecting the interests of or jeopardise the chances of manuscripts GMO foods, the growing trend in anti- those who laboured to collect them. This appearing in peer-reviewed journals. To science rhetoric is alarming and the erosion was evident when the team behind the address these concerns, a series of ASAPbio of the public trust in science must stop! groundbreaking SPRINT clinical trial learned meetings (Accelerating Science and that almost a third of their planned papers Publication in biology) started in 2016 with Replication and reproducibility are core to were at risk of being scooped after the invited stakeholders representing junior and the scientific method, yet several decades NIH and New England Journal of Medicine senior working scientists, funding agencies, of the ‘publish or perish’ mantra have eroded gave competing researchers early access scientific societies, industry, databases and these foundations. According to Nature, for a data-challenge competition. However, journals (asapbio.org/meetings). Since then, more than 70% of surveyed researchers even if they are beaten to the punch on there has been a cascade of major events have been unable to reproduce other subsequent findings, the community will that should quell concerns and encourage scientist’s experiments, though it is feared still await validation of any new results and all life scientists to embrace preprints. First, this barely scratches the surface of the issue. show due deference to the confirmatory Crossref has started accepting preprints A multitude of harmful practices such as studies performed by the original as a content type that it will assign a DOI selective reporting, ‘p-hacking’, inadequately discoverers. However, when the morals and (Digital Object Identifier) to, which in turn detailed methods and limited strategies ethics of situations like these are considered, makes preprints fully citable materials (e.g. to decrease bias have all culminated in an especially for those studies immediately preprints appear regularly in the reference unprecedented replication crisis which feeds pertinent to human health or publicly funded, lists of Nature and Science), enabling version into the ugly spectre of science’s ‘credibility there can be no question that the potential tracking and linkage with the final peer- problem’ (Baker, 2016). for open data to expedite discovery far reviewed version. Second, the world’s largest outweighs the downsides for those that research funders, namely the Wellcome Moving to an open science future may be collected them. Trust, UK Medical Research Council, Howard the only way to stem the tide. In order to Hughes Medical Institute, and the NIH (USA increase scientific literacy and restore trust, In that same vein, open notebook science, National Institute of Health), all announced we must re-engage the public as active the logical extreme of open research, policies to allow researchers to cite their stakeholders. Secrecy breeds suspicion, and argues the benefits of transparency will own preprints in grant applications and as a community, scientists can no longer always outweigh the cost. The practice reports (Luther, 2017). Third, there is a afford to conduct their affairs behind involves placing raw and processed data growing list of journals and publishers that closed doors. Open research offers us an with any associated materials online as it is now no longer consider preprints as ‘prior innovative way to face our problems head-on generated, and explicitly includes making publication’, such as Elsevier, Springer, and restore public confidence in scientific available failed, less significant or otherwise Nature and Wiley, a list which also includes research. typically unpublished experiments. While The Physiological Society’s own publications: most researchers get queasy at the thought The Journal of Physiology and Experimental Open data is a key element of open research, of revealing their work habits and data Physiology. Lastly, after receiving a the profound benefit of which was best with warts and all, scientists studying the $1 million grant and the backing of major demonstrated by the Human Genome Zika virus have been lauded for providing a international funding agencies like the Project. It was the first major initiative to daily-updated online open notebook for their European Research Council, ASAPbio issued encourage the free distribution of research research. Their brave move has paved the a RFA (request for applications) to create data into the public domain, often releasing way for future pioneers of open research a central preprint aggregating service for new DNA sequences within 24 hours of and was accompanied by a joint statement life science similar to PubMed Central. The completion with the initial draft sequence from over 30 global health bodies calling Center for Open Science (COS) with the finally published in 2001. Today there are on all research data gathered during future support of 12 preprint servers (e.g. arXiv, 900+ life science data repositories which public health emergencies to be made bioRiv), 15 repositories (e.g. Mouse Phenome researchers can freely use for reproducing available as rapidly and openly as possible Database, Protein Data Bank, Figshare) and studies, hypothesis testing and data mining, (Islom, 2016). several stakeholders responded to the RFA provided the original source is attributed. with a proposal to set up The Commons.

28 Physiology News / Summer 2017 / Issue 107 References

Baker M (2016). 1,500 scientists lift the lid on reproducibility. Nature 533, 452–454. [DOI: 10.1038/533452a]

Bourne PE, Polka JK, Vale RD, Kiley R (2017). Ten simple rules to consider regarding preprint submission. PLOS Computational Biology 13(5), e1005473. [DOI: 10.1371/journal.pcbi.1005473]

Dingley B (2006). U.S. periodical prices – 2005. American Library Association 45, 1-16. [Accessed 24 May 2017]

Enserink M (2016). In dramatic statement, European leaders call for ‘immediate’ open access to all scientific papers by 2020.Science Magazine – ScienceInsider. [DOI: 10.1126/science.aag0577]

Islom H (2016). Sharing data during Zika and other global health emergencies. Wellcome Trust Blog. [Accessed 21 May 2017]

Knappenberger B (2014). The Internet’s Own Boy: The Story of Aaron Swartz. Participant Figure 5. Open science characteristics and indicators tracked by the European Commission’s Media. Open Science Monitor. Created for European Commission – Open Science Monitor [Accessed 21 May 2017] © OpenStreetMap.org contributors, licensed under ODbL and CC BY-SA 2.0.

Luther J (2017). The stars are aligning for preprints. The Scholar Kitchen. [Accessed 21 May 2017] obvious, its practitioners are few. Seeking Aaron Swartz’s dream of a day when access to change this, the EU-funded FOSTER to the world’s entire scientific heritage is Powell K (2016). Does it take too long to publish research? Nature 530, 148–151. project (Facilitate Open Science Training free to all, as enshrined in article 27 of the [DOI:10.1038/530148a] for European Research) was launched in Universal Declaration of Human Rights. It is

2014 to promote incorporation of open not hard for me to imagine a future where Swartz A (2008). Guerilla Open Access Manifesto. access approaches into researchers’ existing discoveries are routinely documented in [Accessed 21 May 2017] the Amsterdam Call for Action on Open conducted transparently. I can see study Science advocating for an environment where registration reports being used to counteract Teperek M (2017). Piloting more openness at the ‘data sharing and stewardship is the default bias and the publication of replication University of Cambridge. Wellcome Trust Blog. approach for all publicly funded research’ studies and negative results becoming [Accessed 21 May 2017] progress in open science worldwide (Fig. 5). principles of the open science movement, it Recently, the Wellcome Trust and University is only fear of the unknown which holds us Travis J (2016). In survey, most give thumbs-up to pirated papers. Science Magazine – ScienceInsider. of Cambridge have teamed up to run a back. For my part, I will only publish open [DOI: 10.1126/science.aaf5704] two-year, open research, pilot project in an access, deposit my preprints on bioRxiv effort to better understand the barriers to and may even upload completed sections open research (Teperek, 2017). Should the from my lab notebook to Figshare. But more project prove successful, the Wellcome Trust importantly, what steps will you take to and others have promised to put their money realise an open science future? where their mouths are and begin to actively fund cutting-edge open research, which will surely rally more to the cause.

29 Features

Cortisol: often not the best indicator of stress and poor welfare The definitions of the term stress are often confusing and should not be linked to cortisol, which is a valuable welfare indicator, but context is needed to interpret it

The glucocorticoid cortisol is produced in many mammals, such as primates, carnivores and ungulates, and in other animals. Corticosterone has the same function, being produced in rodents and many birds, including poultry, so reference to cortisol below generally applies to corticosterone as well. The hypothalamic–pituitary– interrenal response of fish that experience adversity involves interrenal tissue whose cell functions are very similar to those of the mammalian adrenal gland. Maximal concentrations of cortisol are produced in a trout when it is removed from water and hence deprived of oxygen.

Cortisol in positive and negative The facilitation of learning is clearly a positive situations function, as is the increase in cortisol during courtship, mating and exertion to obtain A key, adaptive function of the food. Whilst cortisol has an adaptive function is to make energy available for the individual when it is produced in in emergency situations, and in some other response to perceived danger, pain or Donald Broom situations where it is needed, but they difficulty to control interactions with the have other important roles. The majority environment, these situations are negative Department of Veterinary Medicine of cells in the human body have receptors and there may be some substantial negative University of Cambridge, UK for cortisol and glucocorticoids reach every consequences of the cortisol, as described organ, thus cortisol has a broad variety of below. Cortisol has roles in both positive effects, including effects on metabolic, and negative situations so it is erroneous to cardiovascular and immune responses. consider it to be always or generally harmful There is a daily fluctuation in the secretion to the individual. of cortisol, and hence in plasma cortisol concentration, beginning in humans with The meanings of stress and welfare a distinct sharp rise of cortisol at the time of waking, followed by a steady decline For most people, stress implies the effects over the course of the day, with the lowest of a challenge to the individual that disrupts levels in the early morning hours. The homeostasis resulting in adverse effects. cortisol facilitates effective learning, via It is not just a that activates the functioning of the hippocampus, and energy-releasing control mechanisms. maintains other normal functions in the body Stimuli whose effects are beneficial would (Broom & Zanella, 2004). Hippocampal cells not be called stressors by most people. Also, actively take up cortisol in vitro. Extreme situations that activate the hypothalamic– adversity can suppress the daily cortisol cycle pituitary–adrenal cortical axis as part of in humans (Kivlighan et al., 2008) and lead a brief emergency response, but whose to less effective hippocampal function and effects are useful to the individual, would hence worse learning ability and memory. not be called stressors by most of the public.

30 Physiology News / Summer 2017 / Issue 107 200

150

100 ‘The context in which Cortisol (nmol/l) changes in cortisol 50 occur is essential L information for 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 interpretation of the Time (h) physiological data’

Figure 1. The concentration of cortisol in blood plasma was measured in two groups of catheterised sheep, after a period of adaptation to the catheters, during a commercial 31- hour journey. The basal concentration was close to 50 nmoles per litre. There was a one- hour stationary period at 15 hours.

The writings of Selye, although stimulating part of welfare. Coping with is useful research, have been scientifically necessary if welfare is to be good so health is confusing in relation to the use of the an important part of welfare. There is a clear term stress. A definition of stress that is relationship between stress and welfare in in line with the general public usage of that, whenever there is stress, welfare will be the word is, stress is an environmental poor. However, welfare could be temporarily effect on an individual which overtaxes poor without any long-lasting adverse its control systems and results in adverse effect, so this would be poor welfare without consequences, eventually reduced fitness, stress (Broom & Johnson, 1993). (Broom & Johnson, 1993; Broom, 2014). According to this definition, there is no good Writings about the concepts of ‘one health’ stress and effects that are called good stress and ‘one welfare’ emphasise that the should be called stimulation. During the meanings of scientific terms concerning development of individuals, stimuli that result humans and non-humans should be the from situations that are somewhat difficult same. However, human usage and definitions for that individual can be useful experience sometimes apply only to humans and there but these are best not referred to as being can be an erroneous assumption that stressful. This definition is similar to that of some mechanisms are confined to humans. Lazarus (2006) who said that stress refers The distinction between physical and to a situation in which demands are perceived psychological stressors may involve the to exceed one’s personal resources. However, assumption that most non-human stress is whilst this definition depends on , solely physical. Dedovic et al. (2009) suggest it is better for the definition to depend on that a stressor facing a wild animal, with the function and to apply to all animals. anticipation of bodily injury, is physical while social evaluative threat would be considered Scientists and legislators now use animal psychological. It has been suggested welfare as a term that is a scientific concept that reactive stressors tend to implicate describing a potentially measurable quality brainstem, specific hypothalamic nuclei of a living animal at a particular time. The and the bed nucleus of the stria terminalis, welfare of an individual is its state as regards which all have direct connections to the its attempts to cope with its environment. paraventricular nucleus whilst anticipatory Welfare can be measured scientifically and stressors, seem to engage limbic system varies over a range from very good to very regions. This is likely to be valid but does not poor. Welfare will be poor if there is difficulty differentiate non-human and human because in coping or failure to cope. There are the brain mechanisms are present in a range various coping strategies with behavioural, of species. A concept of the future and other physiological, immunological and other aspects of are evident from many components that are coordinated from the non-human studies (Broom, 2014). Health, brain. Feelings, such as pain, fear and the welfare and stress are the same concepts in various forms of pleasure, are often part humans and other sentient animals because of a coping strategy and feelings are a key most of the mechanisms are the same.

31 Cortisol as an indicator of stress Long-term problems may be an accumulation and welfare of short-term difficulties in life, each of which is associated with cortisol production. When humans and other animals are Although this production of cortisol is subjected to short-term problems, e.g. essential for survival, after injury or various painful procedures, frightening situations other problems, if it continues to be present such as being picked up or transported, or it can break down the protein in muscle, experiences that cannot be controlled, the inhibit the ongoing replacement of calcium increase in cortisol that usually occurs can in bone and produce myopathy, weakness, be measured and used as an indicator of fatigue and decalcification of bone the extent of poor welfare. In some cases (Melzack, 2001). Frequent, high levels an experimenter can predict that there will of cortisol production may lead to neural References be long-term harm so the individual can be degeneration of the hippocampus, amygdala said to be stressed. Cortisol concentration in and pre-frontal cortex and suppression of Bremner JD (1999). Does stress damage the brain?. blood and saliva and, later, the concentration immune system function (McEwen, 2007). Biological Psychiatry 45, 797–805. of cortisol metabolites in urine, faeces and People with Post-Traumatic Stress Disorder hair increases when a person hits their and other substantial long-term problems Broom DM (2014). Sentience and Animal Welfare finger with a hammer, a rabbit is subjected have hippocampal and other brain damage, (pp. 200). Wallingford: CABI. to a temperature of 42˚C, a calf is loaded some mediated via cortisol (Bremner, onto a transport vehicle, a sheep is driven 1999). High plasma cortisol in elderly men Broom DM, Fraser AF (2015). Domestic Animal th around bends so that balance is difficult, a is associated with lower cognitive ability Behaviour and Welfare, 5 edition. (pp. 472) pig is introduced into a group of strangers, (MacLullich et al., 2005). Glucocorticoid Wallingford: CABI. a salmon is pumped through a pipe, or effects on the immune system may include Broom DM, Johnson KG (1993, reprinted with a wild bird is brought into captivity. The changes in the numbers of leucocytes, corrections 2000). Stress and Animal Welfare (pp. increase can be assessed in relation to suppressing the activity of B-cells and 211). Dordrecht: Springer. the basal cortisol concentration and the cytotoxic T-cells and changing cytokine known maximum increase in such an animal. activity in ways which increase susceptibility Broom DM, Zanella AJ (2004). Brain measures which Provided that the sampling of, for example, to pathogens. These are clearly negative tell us about animal welfare. Animal Welfare 13, blood is not itself the cause of any increase effects on the individual so frequent, high S41–S45. and the time taken for the cortisol increase concentrations of cortisol are indicators of to occur is taken into account, the magnitude stress and poor welfare. Dedovic K, Duchesne A, Andrews J, Engert V, of change gives useful information about the Pruessner JC (2009). The brain and the stress axis: subject’s welfare (Broom & Fraser, 2015). However, some environmental conditions, the neural correlates of cortisol regulation in such as housing conditions that do not response to stress. Neuroimage 47, 864–871. An example of cortisol measurement giving meet the individual’s needs, may not lead useful information about animal welfare is to a change in cortisol concentration. Kivlighan KT, DiPietro JA, Costigan KA, Laudenslager shown in Fig. 1. During a period of monitoring Hence the absence of an increase in cortisol ML (2008). Diurnal rhythm of cortisol during late pregnancy: associations with maternal sheep during a road journey, the sheep concentration does not indicate that there psychological well-being and fetal growth. showed a very marked increase in plasma is no problem for the individual. Many Psychoneuroendocrinology 33(9), 1225–1235. cortisol from the baseline when they were chronic problems lead to attempts to cope loaded on to the vehicle. This occurred not involving cortisol and to other negative Lazarus RS (2006). Stress and : A New despite the fact that the staff concerned effects so a range of welfare indicators is Synthesis. New York: Springer. were experienced animal handlers and did needed to identify that the individual has a not treat the animals roughly. The sheep had problem. This is true of human and non- MacLullich AM, Deary IJ, Starr JM., Ferguson KJ, never before been on a vehicle and were human subjects. Damage to the hippocampus Wardlaw JM, Seckl JR (2005). Plasma cortisol levels, clearly very disturbed by the loading. The and other regions of the brain, clearly an brain volumes and cognition in healthy elderly men. response lasted for 5–6 hours. The cortisol indicator of poor welfare, may be caused Psychoneuroendocrinology 30, 505–515. concentration then dropped to close to the by high-fat diet, alcohol, food restriction or basal level as the sheep became accustomed sleep deprivation with no effects on cortisol. McEwen BS (2007). Physiology and neurobiology to their new environment. It did not change Abnormal behaviour, such as stereotypies of stress and adaptation: central role of the brain. during a one-hour period when the vehicle or high levels of aggression, are sometimes Physiological Reviews 87, 873–904. was stationary. Most of the journey was a very useful indicator of poor welfare in on motorways, but the last 3 hours of the situations where there is no elevated cortisol. Melzack R (2001). Pain and the neuromatrix in the brain. Journal of Dental Education 65, 1378–1382. journey were on side roads with bends at Fluctuations in cortisol may provide no intervals. The drivers drove just as they evidence of poor welfare because they are would with human passengers. However, preparation for courtship or active food- a sheep standing on a moving vehicle has finding. Hence the context in which changes much more difficulty maintaining its balance in cortisol occur is essential information than a human sitting in a seat. Cornering and for interpretation of the physiological data acceleration caused problems for the sheep, (Broom & Fraser, 2015). so cortisol concentration increased. It is clear from studies over relatively short periods, like this one, that measurement of cortisol concentration can provide information about the welfare of animals and help in the formulation of advice about how to avoid welfare problems for the animals.

32 Physiology News / Summer 2017 / Issue 107 Features

Science and politics The 1923 International Physiology Congress in Edinburgh

‘La science n’a pas de patrie, parce que le savoir est le patrimoine de l’humanité, le flambeau qui éclaire le monde. La science doit être la plus haute personnification de la patrie parce que de tous les peuples, celui-là sera toujours le premier qui marchera le premier par les travaux de la pensée et de l’. Luttons donc dans le champ pacifique de la science pour la prééminence de nos patries respectives.’ Louis Pasteur, inaugural speech of the Pasteur Institute, 14 November 1888

The result of the Brexit referendum and the When I was a physiology lecturer at election of President Trump are largely due to Edinburgh University in the late 70s and increased nationalistic feelings in both the UK early 80s, I found, tucked away in the and the US, and there is evidence that these departmental library, a couple of cardboard sentiments are also growing in other parts of boxes containing papers, letters and Europe and the world. Nationalism has always documents related to the organisation of had a challenging relationship with science, the 1923 congress. Unfortunately, neither Fernando Cervero exemplified in extreme by the diaspora of the Physiology Department nor its library German scientists under the Nazi regime; exist today but some of the documents Emeritus Professor, a mass exile which greatly benefited the of the congress were transferred to the McGill University, Canada receiving countries. As we are now being told University main library where they have been that walls will be built and border restrictions safely kept. will be imposed, it is worth having a look at how our predecessors dealt in the past with Going through these records, it is intriguing such problems. to see how some things about congress organisation have not changed in the In 1923, the 11th International Physiological intervening decades whereas others are Congress was held in Edinburgh at the long gone, like the mention in the letter invitation of the then Professor and Chair of invitation to the Lord Provost of of Physiology of Edinburgh University, Edinburgh that ‘we already have an entry Edward Sharpey-Schafer. This was a major of close on 400, which does not include scientific event attended by more than 400 ladies accompanying members’. But physiologists from all over the world among registration letters, requests of (BMJ, 1923). These congresses, first started accommodation, invoices and other such in 1889, were held every 3 years and led to papers, the documentation of the the formation in 1953 of the International congress contains written evidence of a Union of Physiological Sciences (IUPS) key political issue: should scientists from (Schulz-Hofer, 2009). The 1923 congress Germany and Austria be allowed to attend was the second held in the UK, the first one the congress? took place in 1898 in Cambridge.

33 Figure 1. Letter dated 19 January, 1923, from the American Physiological Society supporting the inclusion of all physiologists in the congress (University of Edinburgh library).

Figure 2. Letter from a French physiologist (E Maignon) announcing his boycott to the congress because of the presence of German scientists. There is no mention in the letter of the content of the ‘manifesto’ (University of Edinburgh library).

Figure 4. Registration entry of Juan Negrin who would later become the last Prime Minister of the Spanish Republic before the Franco takeover. (University of Edinburgh library).

Figure 3. A page of the registration book of the congress. Delegates were asked to write their name and address as they registered. Note Sherrington’s entry – 4th from the bottom. (University of Edinburgh library).

34 Physiology News / Summer 2017 / Issue 107 The meeting took place 5 years after the end In another communication they state that of the Great War, and feelings among some ‘the question of receiving guests from attendees were still raw. The sequence of Germany and Austria was considered and it physiology congresses had been interrupted was unanimously agreed that no objection by the war and was only re-established should be raised’. The letter also includes data in 1920 with a congress in that on the accommodation charge: 8 shillings and deliberately excluded physiologists from the sixpence (42.5p in today’s currency) per head recently defeated countries. For the 1923 per night for dinner, room and breakfast. congress, a passionate debate raged as to whether the barring of German scientists Aside from the German-French question the should still be maintained. The debate was congress papers also contain some other ‘They opposed any fuelled by the threat of Belgian and French bits of political relevance. One of the Spanish physiologists to boycott the congress if delegates at the congress was Juan Negrin, ban for reasons of German scientists were allowed to attend. Professor of Physiology at the University of who later in life became finance nationality and invited The Edinburgh organisers, led by Sharpey- minister in the Spanish Republic and was Schafer, wanted to have a truly international appointed Prime Minister during the Spanish physiologists from all congress, stating that science is universal civil war (Fig. 4). Negrin was a physiologist and that all scientists should be allowed turned politician who unsuccessfully tried to over the world to to participate, meet and debate with their save the Spanish Republic from the Franco peers. They opposed any ban for reasons of onslaught and the brutal repression that come to Edinburgh’ nationality and invited physiologists from all followed (Preston, 2016). over the world to come to Edinburgh. In the case of Sharpey-Schafer this was even more On the scientific side, highlights of the poignant as his two sons had been killed in congress included lectures from action in the Great War. He had changed – delivered by his son – on and his name in 1918 from Schäfer to Sharpey- sleep, by Langley on the axon reflex and Schafer after his son John was killed at the a keynote lecture by John Macleod from battle of Jutland. ‘In our family we had to Toronto on recent research on insulin from mourn the loss of my elder and only surviving his laboratory. Interestingly, Frederik Banting, son John Sharpey (Jack) … I decided to add co-worker of Macleod and co-discoverer the name Sharpey to my own name and duly of insulin, or perhaps just discoverer advertised the fact. I did this partly on Jack’s depending who you believe, was also account, partly because it was the name attending the congress but Macleod got the References of my old teacher & master of Physiology limelight of the keynote lecture. Both were (William Sharpey) – the best friend I ever had’ awarded the Nobel Prize in 1923 only a few British Medical Journal (1923). July 28, p. 142; , p. 201; August 11, p. 256. (Sharpy-Schafer diaries). months after the congress and there is a considerable literature as to the respective Schulz-Hofer I (2009). IUPS, a family of physiologists. The American Physiological Society achievements of either of them as well as to int.physiology.jp/download/4736/file.pdf endorsed the aim of the organisers in a letter the contributions of Charles Best to whom addressed to Sharpey-Schafer (Fig. 1) stating Banting gave half of his prize money and EA Sharpey-Schafer diaries, Sharpey-Schafer that ‘science knows no creed’ and extending James Bertram Collip who in turn received Papers, Wellcome L., London, PP/ESS/S.1-3, S.2, their support to the organizing committee from Macleod half of his cash S.3 (microfilm). http://www.npg.org.uk/collections/ to ensure a truly international congress. (www.nobelprize.org/educational/ search/personExtended/mp04073/sir-edward- However, French and Belgian physiologists medicine/insulin/discovery-insulin.html). sharpey-schafer?tab=biography were less forgiving and some decided not to attend the congress in protest for the Turning back to the question of science and Preston P (2016). The last days of the Spanish presence of German physiologists (see Fig. 2). politics, it is refreshing to see the efforts Republic. London: William Collins. But in the end the congress was a success made by Sharpey-Schafer and his committee and was attended by la crème de la crème of as well as from organisations such as the www.nobelprize.org/educational/medicine/insulin/ contemporary physiology including Adrian, American Physiological Society to ensure discovery-insulin.html Banting, Bayliss, Dale, Einthoven, Frank, von a truly international congress, to remove Frey, Fulton, Gasser, Haldane, Hill, Houssay, barriers imposed by nationality and to build Langley, Pavlov, Sherrington and Szent- goodwill among fellow scientists. His own Gyorgyi among others (see Fig. 3). personal tragedy did not prevent him from achieving this aim. A lesson to us all. The congress papers contain some gems regarding the sensitive issue of the German delegates. Two letters from the Edinburgh Acknowleldgements Association for the provision of Hostels for Women Students include some interesting My thanks to Dr Graeme D Eddie, Assistant sentences regarding the accommodation that Librarian, Archives & Manuscripts, Edinburgh they were offering for congress delegates. University Library for finding the congress In one of them they state that the hostels documents and to Tilli Tansey OBE for helpful ‘will endeavour to divide the Germans advice and comments on this article. from the French’ hoping that they would ‘understand a sufficient amount of English’.

35 Features

What does the future hold for research into Epithelia & Membrane Transport? What is the most important property of an epithelium?

As a PhD student I was asked the question: ‘what is the most important property of an epithelium?’ I tried my best to recite some typical textbook phrases like how it acts as a selective barrier to the external environment and its transcellular transport capabilities. On all counts I was wrong – the answer my superior was looking for was that ‘the cells are polarised’.

Some 10 years on, I cannot help but wonder approaches to overcome inflammatory what answer I would receive to this same diseases affecting the intestinal and question if I were to ask a PhD student in an respiratory mucosa. Indeed new insights into epithelia research lab today. Of course, some the innate immune signalling or potential may indeed still answer ‘epithelial polarity’, phagocytic capacity of epithelial cells could James Garnett but possibly for less obvious reasons than even see epithelia classified in physiology the distinct plasma membrane domains textbooks of the future as a type of immune Boehringer Ingelheim, Germany, allowing directional transport of molecules cell. Beyond the well-studied tight and and Newcastle University, UK across the epithelium. In cancer research, adherens junctions, new innovations in loss of epithelial polarity marks the beginning microscopy are expanding our understanding of epithelia-to-mesenchymal transition in of epithelia cell–cell communication such as which cells acquire migratory and invasive how deep nuclear invaginations form tunnels capabilities, promoting metastasis in traversing the nucleus and encasing the epithelium-derived carcinoma. A student cytoskeleton, providing a physical/mechanical in an epithelial barrier lab may also give link from the nucleus to desmosomes at the this answer but in the context of epithelial cell membrane. wound healing, where epithelial polarity defines cellular differentiation vs proliferation And all this before one even begins to potential. And in an infectious disease lab the consider the possibilities of future research same answer could be used to point to how into epithelial membrane transport, an certain bacterial pathogens are capable of exciting field of research that has provided reversing epithelial polarity as a mechanism new therapies for many diseases and most of penetrating the epithelial barrier. notably in recent years has provided the closest thing to a cure for a small subset of My guess would be that many would give Cystic Fibrosis patients through insights into much more diverse answers to this question, the regulation of the CFTR ion channel. New and I can only imagine what might be insights into novel aspects of the regulation Morag Mansley considered the most fundamental properties of membrane transporters and channels, of an epithelium in another 10 years’ time. In such as the study of extracellular vesicles, The University of Edinburgh, UK the context of the epithelium as a protective may represent the next major breakthrough barrier against pathogens, new research into in the identification and treatment of the Co-convenors of the Epithelia and barrier properties and host–microbiome numerous disease states in which ion and Membrane Transport theme crosstalk could provide innovative alternative solute transport become dysregulated.

36 Physiology News / Summer 2017 / Issue 107 ‘The study of extra- cellular vesicles may represent the next major breakthrough in the identification and treatment of the numerous disease states’

Figure 1. Extracellular vesicle (ECV) biogenesis and interaction with recipient cells. Figure used with permission from Morrison et al. (2016).

Extracellular vesicles: novel regulators spanning the length of the nephron are the more classical hormone/- of epithelial transport? capable of releasing these vesicles (Pisitkun mediated regulation of epithelial transport? et al., 2004). Analysis by mass spectrometry The potential for cellular signalling along One of the defining features of a polarised revealed these ECVs contained a variety the length of the nephron via ECVs in the epithelium is its ability to transport a variety of proteins including tubular transporters ultrafiltrate certainly seems plausible and of different ions and solutes, as well as as well as proteins involved in membrane may indeed be of great relevance. water. This occurs via transporters and ion trafficking. Interestingly, analysis of ECVs in channels differentially expressed within urine collected from patients with Bartter distinct apical and basolateral domains of the Syndrome Type 1 showed a complete plasma membrane. absence of the Na-K-Cl co-transporter 2 (NKCC2), revealing a potential use of ECVs as References Membrane transport across epithelial tissues biomarkers of disease (Gonzales et al., 2004). is subject to regulation by a wide variety of Indeed, biomarkers in urinary ECVs have been Gonzales PA et al. (2009). Large-scale proteomics and phosphoproteomics of urinary exosomes. and bioactive factors, which can proposed across the entire spectrum of renal Journal of the American Society of Nephrology either upregulate or downregulate transport disease (Morrison et al., 2016). The value 20, 363–379. [DOI: 10.1681/asn.2008040406] processes. For instance, in response to of these potential biomarkers remains to be increased plasma osmolality, release of determined, and only large-scale population Gracia T et al. (2017). Urinary exosomes contain the peptide hormone vasopressin studies will reveal if these will be of clinical microRNAs capable of paracrine modulation of (AVP) promotes water reabsorption by use in the future. tubular transporters in kidney. Sci Rep 7, 40601. inserting water channels within the renal [DOI: 10.1038/srep40601] collecting duct. These regulatory processes In terms of intercellular signalling, studies in typically involve receptor-mediated signal renal epithelial cells have demonstrated that Morrison EE, Bailey MA, Dear JW (2016). Renal transduction with resulting alterations to cells not only release ECVs, they can also extracellular vesicles: from physiology to clinical number and/or activity of transporters. take up ECVs. Importantly the contents of application. J Physiol 594, 5735–5748. these vesicles can be transferred, as shown [DOI: 10.1113/jp272182] A novel route of cellular signalling has by the incorporation of ECVs with functional received a great deal of interest recently, AQP2 water channels, collected from AVP- Oosthuyzen W et al. (2016) Vasopressin regulates extracellular vesicle uptake by kidney collecting duct namely the release of extracellular vesicles stimulated donor cells, into unstimulated cells. Clin J Am Soc Nephrol 27, 3345–3355. (ECVs) from cells. These nano-sized vesicles recipient cells (Street et al., 2016). In [DOI: 10.1681/asn.2015050568] are released from nearly all cell types including addition to the transfer of transporter and immune cells, as well as proteins, there is now evidence that ECVs Pisitkun T, Shen RF, Knepper MA (2004). epithelial cells. ECVs are typically classified by contain micro RNAs (miRNAs) which can Identification and proteomic profiling of exosomes their size, origin and identifying markers, and alter epithelial transport (Gracia et al., 2017; in human urine. PNAS 101, 13368–13373. multiple methods are now well established to Oosthuyzen et al., 2017). Interestingly, the [DOI: 10.1073/pnas.0403453101] isolate and identify ECVs (reviewed recently targets of identified miRNAs are not only the in J Physiol; Morrison et al., 2016). ECVs transporters themselves, but intracellular Street JM et al. (2011). Exosomal transmission of have been proposed to carry cargo including kinases known to regulate them. functional aquaporin 2 in kidney cortical collecting proteins, lipids and RNA which upon release duct cells. J Physiol 589, 6119–6127. from the donor cell can be transferred and The physiological relevance of this form of incorporated into a recipient cell (Fig. 1). cellular signalling remains to be determined. In what context does ECV signalling become The identification of ECVs in human urine important? Moreover, what additional samples demonstrated that epithelial cells control does ECV signalling exert alongside

37 Features

Stressing out the immune system Many systems in the human body are impacted by stress, among these the immune system is particularly sensitive

Stress 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 and ill-health.

In the 1970s, Holmes and Rahe developed Defining stress a scale to subjectively grade stress. They ranked over 40 different types of life Stress is highly subjective. Something that I stressors, such as the death of someone may class as stressful (watching Arsenal this Natalie Riddell close to you, changes in relationship status, season), may not be stressful to other people work-related stress, even Christmas, and (Tottenham supporters). So how can we School of Biosciences and Medicine, they assigned each stressor a score. The define stress? In the 1960s, the University of Surrey, UK total tally of stress scores that a person introduced the concept that had experienced in the last year could stress is a process consisting of three distinct accurately predict the likeliness of future steps. First, a stimulus (i.e. the stressor) illness. This demonstrated that stress and has to be present and perceived. Second, illness were closely related. In the 1990s, the stimulus initiates a conscious or sub- Cohen et al. eloquently demonstrated that conscious appraisal whereby the stressor increased the rates of is evaluated in relation to available coping respiratory infections and clinical symptoms options. If the demands of the situation in participants inoculated with the common outstrip the ability to cope then the situation cold (Cohen et al., 1993). Subsequent studies is perceived as stressful. Third, this results revealed that every organ, tissue and cell in a stress response involving emotional of the immune system could be altered (e.g. anxiety, embarrassment) and biological by psychological stress. The involvement (e.g. autonomic-endocrine) adaptations. of immune alterations in stress-induced Put simply, stress is a situation or event diseases was recognised and the field of that exceeds, or is perceived to exceed, the psychroneuroimmunology (PNI) was born. individual’s ability to cope, that then triggers an emotional and biological response.

38 Physiology News / Summer 2017 / Issue 107 Cortisol and adrenaline are released continuously according to a circadian rhythm, thus altering immunity on a daily cycle Image credit: Darryl Leja, NHGRI

The stress adaptation response and development of stem cells into early immunity immune progenitor cells in the bone marrow, through to the instigation of programmed The biological adaptation to stress is immune responses to specific antigens in the activation of the sympathetic nervous lymph nodes. Even when in the peripheral system (SNS). The same biological response is tissues, such as the skin or gut, where mature induced whether the stressor is psychological, immune cells are most likely to encounter such as anxiety or embarrassment, or infections, the cells can be regulated by physical, for example, exercise, trauma or stress hormones. It is therefore unsurprising fever. In the case of psychological stress, the that the immune system is a modifiable ‘Subsequent studies individual perceives an inability to cope and target of stress. revealed that every this results in the amygdala, a part of the brain that contributes to emotion processing, Acute stress and immunity organ, tissue and cell of sending a distress signal to the hypothalamus. The hypothalamus can communicate with the Research often focuses on chronic the immune system periphery via the two arms of the autonomic psychological stress. However, one of the nervous system: the parasympathetic ‘rest most comprehensive meta-analyses on stress could be altered by and digest’ arm and the sympathetic ‘fight or and immunity in humans to date found that flight’ arm. During stress the SNS is triggered the most robust and replicable findings in PNI psychological stress’ and various physiological changes occur, are associated with stress responses lasting including an increase in heart rate, respiration just minutes or hours rather than months or and energy production. This promotes years (Segerstrom and Miller, 2004). A key survival of the individual by maximising phenomenon during acute stress is the rapid physical capacity to cope with the stressor. and transient movement of immune cells into the peripheral blood. But not all immune The SNS innervates many organs and tissues cells are mobilised; only cells which display throughout the body including the adrenal immediate effector functions are involved, gland. During stress, sympathetic signalling such as cytotoxic cells and cells with the causes the adrenal gland to secrete the potential to migrate into inflamed tissues. two main stress hormones: adrenaline and Therefore, acute stress not only increases the cortisol. These hormones can spread and number of immune cells in the blood, but it act throughout the body via the circulation. also changes the composition of the blood. The SNS innervates all of the organs of the The upshot is an increase in the circulating immune system, and individual immune cells ‘soldiers’ of the immune system, which is also express adrenergic and glucocorticoid proposed to increase immune surveillance and receptors, so can directly respond to thus enhance immunity during times of stress changes in circulating levels of adrenaline when, historically at least, injury and infection and cortisol. Stress is therefore able to alter were more likely (Dhabhar, 2009). every process of immunity, from the initial

39 It is indeed unlikely that the in an individual who has an underlying of stress adaption would select for a inflammatory or autoimmune disorder, cardiovascular and metabolic system that such as atherosclerosis. The promotion of helps the organism to rapidly escape a immunity in these circumstances could be predator, only for it to later succumb to an seen as a negative outcome that would infection. aggravate the condition.

Indicative of an evolved ability to rapidly Chronically stressing a caveman adapt to danger, all vertebrates, including humans, have the remarkable capacity to What if the stress lasts for weeks, months ‘Stress is therefore able swiftly alter the immune cell composition or years? The stress adaptation response in peripheral blood and tissues in response did not evolve to last for extended periods to alter every process to acute stress. Furthermore, experimental and, consequently, it cannot. This was first animal studies have confirmed that recognised in the 1930s by Hans Selye who of immunity, from the acute stress, and the accompanied cell described the three stages of the General redistribution, predicts stronger delayed- Adaptation or Stress Syndrome. First there initial development of type hypersensitivity responses, enhanced is the acute stress response in which the vaccine responses, an increased migration of body prepares for fight or flight. But this level stem cells ... through leukocytes into wounded tissue, and faster of excitement cannot be maintained so a wound healing. In humans, brief psychological second stage of adaptation occurs where the to the instigation of stressors and exercise prior to vaccination body becomes resistant to the stress. Finally, programmed immune have also demonstrate the ability to increase in chronic stress, the system enters a state vaccination-induced antibody responses of exhaustion and this fatigue of the immune responses’ (Dhabhar, 2009). system results in illness.

But how do the physiological effects of One theory in is acute stress manifest now in the modern that we have a Stone Age brain. This does era, when stress does not usually come not mean the brain has not evolved since the with a physical or immunological challenge? Stone Age, but that the brain has not evolved Imagine increasing immune-surveillance quickly enough for the modern world.

Our response to stress may reflect that we have a so-called Stone Age brain, that it hasn’t evolved quickly enough to adapt to modern day stressors

40 Physiology News / Summer 2017 / Issue 107 This may be true for the response to Stress and circadian rhythms present-day stress. Many of today’s life stressors that cause an emotion response in Cortisol and adrenaline are not only released the amygdala do not require a physiological in response to stress – they are released response to ensure survival of the individual. continuously and have circadian rhythms, Considering this, it is not surprising that the their diurnal fluctuations altering levels of stress adaptation response to chronic stress immunity dependent on the time of day. may not serve us well. For example, the number of effector T-cells Chronic stress and immunity with immediate protective capacity in the circulation peak during active hours whilst The immune system is delicately balanced naïve cell numbers are greater nocturnally. References between immune activation, which will clear This rhythmicity is thought to promote infections and malignancies, and immune immediate immune protection during Bosch JA, Fischer JE, Fischer JC (2009). Psychologically regulation which prevents self-harm that the day, and tissue repair and initiation of adverse work conditions are associated with CD8+ T could otherwise result in autoimmunity adaptive immune responses at night. Immune cell differentiation indicative of immunesenescence. and inflammatory disorders. Chronic stress circadian rhythmicity has clinical implication Brain Behav Immun 23(4), 527–534. appears to disrupt this balance. It causes as demonstrated by a greater risk of death the worst of both worlds: lower immune from sepsis in the early hours of the day, and Cohen S, Tyrrell DA, Smith AP (1993). Negative protection and greater inflammation. Cross- the recent finding that vaccinations given life events, perceived stress, negative affect, and sectional studies of dementia caregivers during morning clinics may produce better susceptibility to the common cold. J Pers Soc Psychol 64(1), 131–140. versus age-matched non-caregiver controls antibody responses (Long et al., 2016). demonstrate that chronic stress clinically These observations signify the importance Dhabhar FS (2009). Enhancing versus suppressive reduces humoral (B-cell and IgG antibody) of the immune system’s circadian rhythm. effects of stress on immune function: implications and cell-mediated (T-cell) immune responses One of the negative consequences of for immunoprotection and immunopathology. to vaccination (Gouin et al., 2008). Caregivers stress is that it may alter the typical daily Neuroimmunomodulation 16(5), 300–317. also report more days of illness and upper perturbations of cortisol and adrenaline, respiratory tract infections. Together, this and therefore alter normal immune Gouin JP, Hantsoo L, Kiecolt-Glaser JK (2008). suggests that stress causes a decrease in homeostasis. This will particularly effect the Immune dysregulation and chronic stress among immunity to novel infections. Chronically health of individuals working night-shifts or older adults: a review. Neuroimmunomodulation stressed individuals also show slower wound travelling between different time zones on 15(4-6), 251–259. healing, latent virus reactivation, shortened a regular basis. leukocyte telomere lengths, greater oxidative Long JE et al. (2016). Morning vaccination enhances stress and increased low-grade systemic Managing stress antibody response over afternoon vaccination: inflammation, including increased IL-6. These A cluster-randomised trial. Vaccine 34(24), 2679–2685. effects can be seen in both young and old Even if we could stop it, preventing the caregivers, individuals effected by major life stress adaptation response from occurring Segerstrom SC, Miller GE (2004). Psychological events, and from individuals self-reporting during a true physical threat to a person stress and the human immune system: a meta- high levels of stress. could be dangerous and leave them analytic study of 30 years of inquiry. vulnerable to infection. But as stress only Psychol Bull 130(4), 601–630. Stress, immunosenescence and occurs when a person believes they cannot age-related diseases cope, we can teach and resilience. Social support is essential for The similarities of immune dysfunction good psychological health and resilience. brought about by ageing and chronic Caregivers with greater support demonstrate psychological stress are striking and include better immune outcomes, and stress increased inflammation, reduced vaccination management interventions with caregivers responses, decreased cell telomere lengths can raises vaccination responses to the and increased inflammation (Gouinet al., levels seen in aged-matched non-caregivers 2008). Moreover, like stress, these features (Gouin et al., 2008). Further, in older of immunosenescence have been associated adults, relaxation techniques and stress with an increased risk of morbidity and management interventions can reduce the mortality. It is possible that chronic stress signs of herpes virus reactivation. These may exert its negative impact on health results demonstrate that social intervention through the induction of immunosenescence. and stress management techniques can High levels of work-related stress have been buffer the negative impact of stress on associated with rudimentary signs of immune immune outcomes. Preventing stress may ageing (Bosch, Fischer et al., 2009). Further, therefore be an easy and affordable way, the impact of stress on immune function compared to most medical interventions, is reported to be worse in older individuals to improve immune function and thereby suggesting that the elderly are susceptible to improve the general health of the population a cumulative immune deterioration brought and avert disease. about by age and stress. Considering that 25% of the of the UK population is predicted to be over 65 years of age by 2030, a large number of people may be subjected to ill- health by means of stress- and age-induced immune decline.

41 Membership

The dangers of careless press releases The Science Media Centre may help minimise faulty reporting

You open the morning paper and are excited Frustrated by the misrepresentation of to find an article about a newly published obesity in the press, I decided to sign up study in your area of interest. You start to the Science Media Centre (SMC), not reading it and quickly realise that the journalist knowing it would lead to my television debut. has completely taken the press release out of context. What was originally some preliminary The remit of the SMC is to provide journalists cell culture work has turned into a front page with expert quotes on scientific studies that splash solving an age-old problem or heralding are likely to garner media attention. In the a new cure. Sound familiar? world of obesity and diabetes, this usually involves studies showing that eating too We live in a world of 24-hour rolling news much of X will lead to diabetes, or that cutting coverage. The necessity to write punchy news Y out of your diet reduces body weight. headlines and be the first to break stories has never been greater. Because of this, it’s very I recently commented on a new study, easy for journalists to take press releases out which had followed approximately 20,000 of their original scientific context, and ‘sex’ children over a 10-year period, some born via them up in a way that sells. This is particularly caesarean and some born naturally, and found the case for my own area of research, obesity. that those who were born via caesarean were more likely to be obese in later life. I The world is suffering from an obesity was asked to comment whether or not the epidemic especially (but not exclusively) in conclusions of the study were sound, and Simon Cork the Western world. Reports suggest around offer a possible explanation for the findings. two-thirds of people are dieting at any one In fact, this study adds to other literature Imperial College London, UK time, and most of these diets don’t work. supporting this relationship, and the most This is why stories about miracle weight loss likely cause is exposure to different microbes cures and therapies are cat nip to journalists when born naturally versus via caesarean, and readers alike. although the link hasn’t fully been proven. Image credit:Jeff 2.0) Eaton BY-SA (CC

42 Physiology News / Summer 2017 / Issue 107 The Society welcomes our new Treasurer, Frank Sengpiel

In 2000 I was lured back to the UK to take up a senior lecturer position at Cardiff University. Seventeen years later I am still at Cardiff, by now Professor of Neuroscience and Head of the Neuroscience Division in the School of Since the study used a large cohort, the Biosciences. results were more statistically significant. However, since it was an observational study My first encounter with The Physiological there isn’t a causative link. Society was as a PhD student, at meetings which, in those days, were held My comments were picked up by a number at university physiology departments. of news agencies, including The Guardian, I remember them as quite intimidating Daily Mail and the BBC News website. Nerve- affairs, because of the voting by members rackingly, I even got a call from the producer on whether the communication was of BBC Radio 4’s Today Programme, who to be published or not. I later became was interested in picking this piece up and an Associate Member, benefiting from wondered if I would pop into the studio the generous travel grants, and then a Full next morning. This was swiftly followed by Member in 2001. I soon took over Sky News, Jeremy Vine and BBC News. from Kevin Fox as convenor of the Frank Sengpiel Development & Plasticity Special Interest Now all of this was a far cry from the ELISA Group. This was followed by a term as that I was planning on carrying out that day, Cardiff University, UK Theme Lead for Cellular & Integrative but was an interesting insight into the angle Neuroscience from 2009 to 2014. In journalists take on scientific stories. Having 2015 I was elected as a Trustee, and I received the call asking if I’d like to go on the Although I describe myself as a joined the Finance Committee last year. Today programme at 11 pm the previous now, this job description evening, I spent a number of hours doing a did not even exist when I started I have a long-standing interest in financial comprehensive PubMed search of all the most studying for a Diploma in Biology at the matters, which may be rooted in family recent meta-analysis studies investigating Ruhr University in Bochum (Germany) history, since my grandfather, my father, caesarean births and obesity risk. Turns out all in the mid-1980s. Instead, for 2 years and my brother have all worked in the they’re really interested in is why. If the Brexit I learned about zoology and botany, financial sector. However, my practical debate has taught us anything, it’s that the about statistics and organic chemistry. experience so far has been limited to public switch-off at the sight of a percentage A module on animal physiology (in dabbling in investment funds and reading symbol or talk of numbers. What people want those days involving actual frogs rather the money pages in the newspaper that to know is why and how it affects them. So than computer simulations) kindled my everyone else discards! I am very glad my interviews mostly revolved around why interest in how the body works, which to say that I did not receive a note from caesarean births seem to increase the risk was soon narrowed down to how the Anne King saying there is no money left; of obesity and whether there is anything we brain works when Klaus-Peter Hoffmann on the contrary, the balance sheet is can do to mitigate the risk. That and trying to was appointed the first professor of looking very healthy, with a successful politely convince a caller to the Jeremy Vine neurobiology. In 1990, I moved to the property strategy and an excellent Show that her child’s obesity was probably UK for the first time, to study for a DPhil publishing deal as major contributing more the result of her confessed feeding of with Colin Blakemore at the University factors. My aspiration is of course to build copious amounts of chocolate to him, rather of Oxford. My focus on mechanisms of on this, although ‘past performance is no than his method of birth. binocular integration and plasticity of guarantee of future results’! The biggest the visual cortex started at this time and threat, which I do not need a crystal ball If, like me, you find yourself at odds with has stayed with me ever since. Following to see, is Brexit and the uncertainty in journalistic reporting of science stories, I nearly 3 years as a Junior Research Fellow the financial markets that it has already would urge you to join the database at the at Magdalen College I left Oxford in 1996 started to cause. But, in partnership Science Media Centre. You’re not guaranteed to become a research associate in the with our COO and finance committee, to get TV time, but you might get your group of Tobias Bonhoeffer at the Max I am confident that we will steer The name in the paper. Just make sure that you Planck Institute of Neurobiology Society through the next 4 years without at least know enough about whatever it is near Munich. suffering shipwreck. you’re commenting on to make it through a 30-minute conversation with Jeremy Vine and John Humphrys!

43 Membership

How many Members of The Society have won the Nobel Prize?

All academic organisations do it nowadays: questions: ‘How many Members of The claim numerous luminaries, Nobel laureates Society have won the Nobel Prize?’ and and Fellows of this, that or the other, as staff, ‘How many Nobel laureates have been former staff or students, to enhance the Members of The Society?’ I took myself off perception of their lecture theatres and labs to the Archives, with lists of all Nobel Prize as portals to great distinctions and honours. winners to date (www.nobelprize.org/ For example, those walking along the Strand nobel_prizes/lists/all). I have searched in London are assailed by photographs of through more than a century’s worth of the Great and Good alumni of Kings College Grey Books (the much valued membership that include many familiar names from St lists of The Society), a sample of Committee Thomas, Guys, Queen Elizabeth College, minutes, several Secretaries’ correspondence etc, all institutions now absorbed under the files, usually incomplete, various candidates’ banner of KCL (www.kcl.ac.uk/aboutkings/ books, and numerous boxes and folders history/nobellaureates.aspx). My own dating from 1901. None of these is University, QMUL (Queen Mary University completely reliable: the Grey Books never of London), lays claim to Nobel Prize winning appeared on a regular annual basis and the physiologists Henry Dale and , archival collection of what was published is on the grounds that although ultimately partial; Committee minutes, especially until Cambridge medical graduates, both were comparatively recent times, are infuriatingly clinical students at Barts Hospital, now a inconsistent: events and decisions are constituent part of the medical faculty of not always recorded, and the enactment Tilli Tansey QMUL. Additionally, QMUL lays claim to of recorded decisions are not always , who joined Barts Medical College reported; the Secretary’s correspondence Honorary Archivist, The Physiological after getting the Nobel Prize in Physiology is astonishingly varied – some files contain Society & Professor of the History of or Medicine in 1982. Dale, Adrian and Vane extensive and animated correspondence Modern Medical Sciences, QMUL, UK also belong to a small, select sub-group about the price of dinner, but there is little of laureates: they were Members of the consistent correspondence with Members Physiological Society. who had won the Nobel Prize.

How big is that group? The question is not as Searching through all these sources, there straightforward as it might seem. Does one appear to be at least 61 Nobel laureates, in count only Ordinary Members? What about Physiology or Medicine (n=55), Chemistry Honorary Members or former Members who (n=5) or Peace (n=1), who have been then win the Prize? And non-Member Nobel Members of the Physiological Society. laureates who are then offered Honorary They divide, as expected, into two broad Membership, do they register? And how does categories: those who were Members one find all the relevant names since 1901 of The Society before winning the Nobel when the Nobel prizes were first awarded. Prize (n=31), and Nobel laureates who Surely there must be a ‘List’ somewhere? Well were elected to The Society, principally as if there is, I haven’t found it, at The Society’s Honorary Members (n=30). headquarters, in the Archives nor in the memories of senior Members of The Society. Both groups contain interesting anomalies and some unexpected names. A recent press release asserted ‘Since its foundation in 1876, [The Society] has boasted Members of The Society who won 20 Nobel Prize winners’ (www.physoc. the Nobel Prize org/news/2016/physiological-society- announces-new-chief-executive), but in These are predominantly Ordinary a quick back-of-the-envelope calculation Members of the Society, those elected I produced over 30 names without really at a comparatively young age, regularly trying. So to arrive at some definitive attending scientific meetings, presenting number, and to answer those related Communications and Demonstrations to

44 Physiology News / Summer 2017 / Issue 107 Table 1. Ordinary Members of The Physiological Society who won the Nobel Prize PoM = Physiology or Medicine; Chem = Chemistry; (a) = Affiliate

Year Prize Winner Member Hon. Mem.

1920 PoM (1874–1949) 1913 1938

1922 PoM (1886–1977) 1912 1960

1923 PoM John Macleod (1876–1935) 1912

1929 PoM Frederick Gowland Hopkins (1861–1947) 1892 ‘There appear to be at

1929 Chem Arthur Harden (1865–1940) 1904 least 61 Nobel

1932 PoM Charles Sherrington (1857–1952) 1885 1935 laureates, in Physiology

1932 PoM Edgar Adrian (1889–1977) 1917 1960 or Medicine (n=55),

1936 PoM Henry Dale (1875–1968) 1900 1951 Chemistry (n=5), or

1937 PoM Albert Szent-Gyorgyi (1893–1986) 1929 Peace (n=1), who have

1938 PoM (1892–1968) 1931 1967 been Members of The

1944 PoM Herbert Gasser (1888–1963) 1924 1949 Physiological Society’

1945 PoM (1898–1968) 1925 1965

1949 Peace John Boyd Orr (1880–1971) 1918

1953 PoM (1900–1981) 1948

1959 PoM (1915–1987) 1941 1975

1963 PoM (1914–1998) 1938 1979

1963 PoM (1917–2012) 1942 1979

1963 PoM John Eccles (1903–1997) 1929 1982

1967 PoM (1900–1991) 1932 1968

1970 PoM (1911–2003) 1940 1979

1970 PoM (1905–1983) 1937 1972

1982 PoM John Vane (1927–2004) 1953 1988

1988 PoM James Black (1924–2010) 1962 1989

1991 PoM (b.1944) 1981 (a) 1997

1991 PoM (b.1942) 1990 (a) 1997

2008 Chem Roger Tsien (1952–2016) 1974 (a) 2011 the Society, and often serving on Society Ordinary Members of The Society became committees and editorial boards. Table 1 lists Nobel laureates. They include the Hungarian all the names in this category, in order of the Albert Szent-Gyorgyi; the Belgian Corneille year of Nobel Prize – it contains some of the Heymans, and the Swedes Ragnar Granit best-known names in modern physiology. and Ulf von Euler; John Eccles and Howard Florey from Australia; Erwin Neher and Bert Whilst space precludes describing each Sakmann from Germany; and Herbert Gasser laureate and his work (and yes, they are all and Roger Tsien from the USA. In total, there men), some general themes and specific are 11 foreign physiologists, most of whom illustrations are instructive. Intriguingly, for having joined The Society when they were example, the first Ordinary Member to win students, fellows or visitors working in the was a foreign physiologist, August Krogh UK, and many continuing to attend Society from Denmark, and several other foreign meetings whenever in the UK.

45 The first ‘home-grown’ laureate was AV of vitamins, but I can find no evidence In 1909, the very first Nobel laureate Hill who shared the 1922 prize (awarded in that he was ever proposed for Honorary non-Member to be elected to Honorary 1923) with Otto Meyerhof (of whom more membership. membership was the Russian physiologist later) for his work on heat production by Ivan Pavlov (NP 1905 for his work on muscle fibres, followed by Scotsman John However, for many years there was a gastric secretion), and he was followed in Macleod who controversially shared the restriction on the number of Honorary 1918 by (NP 1913), Willem 1923 prize with (of whom, Members, as will be discussed below, which Einthoven in 1924 (laureate the same year) likewise, more later) for their discovery of may account for some of these lapses. And and Ramon Y Cajal in 1931, 25 years after insulin. Since then, a further 13 (including the the delay in Nobel laureates being offered his Nobel award in 1906. Only 12 Honorary German-born, British-naturalised Sir Hans Honorary membership was sometimes due Members were then allowed at any one Krebs and Sir Bernard Katz, both of whom to the individual concerned: Sir Henry Dale time, a maximum of six of whom could be did most of their Nobel winning work in the (NP 1936) was first proposed for Honorary resident in the UK. That restriction had UK) British Members of The Society have status in 1942, although some colleagues been lifted, however, when nearly 60 years been so honoured. From the 1920s onwards, suggested that he would not appreciate later, an occasion arose when there were not a decade of the twentieth century the honour, seeing it as acknowledgement Nobel laureates in what might be termed passed without one or more Ordinary of his retirement from active science and ‘mainstream physiology’ who were not Members of The Society travelling to involvement in The Society (Dale holds already Members or Honorary Members of Stockholm. Many also received high civic the record for serving on the Committee The Society. Thus in 1983, both David Hubel Honours, such as knighthoods and peerages, for 24 years, for most of which he was and were elected 2 years and served in some of the most important Chairman). Discrete enquiries confirmed after their Nobel awards. A curious situation, offices in British science, including the this suspicion and it was only in 1951 that however, relates to one physiological laureate. Presidency of the Royal Society: Hopkins, he eventually accepted, 15 years after his (b. 1925), who was co- Sherrington, Dale, Adrian, Florey, Hodgkin Nobel Prize. Others had even longer delays, laureate with and and Huxley, each of whom also received the although whether through choice cannot be in 2000 for their discoveries concerning . determined without more research. signal transduction in the nervous system. Kandel was elected an Honorary Member Although the majority of these awards were Honorary Members who won the in 2008, and Carlsson the following year. in Physiology or Medicine, there were three Nobel Prize Committee minutes clearly record Greengard in other categories. In 1929, Sir Arthur being nominated in 2009 (along with Harden (member 1904) won the Chemistry A small, even more select group of Society laureates Carlsson, Hunt, Axel and Evans) but Prize for his work on fermentation, and Members who won the Nobel Prize (all for he was never elected. Why? What happened? almost 80 years later in 2008, Roger Tsien Physiology or Medicine) are five foreign Did he not get the invitation, or did he refuse? (Affiliate Member 1974) won the same Prize physiologist whose work and contributions One former Society President recalled: for his work on Green Fluorescent Protein. were recognised by election to Honorary More unusual, however, is the award of membership, before their Nobel awards ‘I cannot remember any actually turning the 1949 Peace Prize to the nutritionist (Table 2). The first in this category was the offers down – but then these people are so Sir John (later Lord) Boyd Orr for his work bacteriologist in 1903, and he shell-shocked that it is harder to decline a as Director-General of the United Nations went on to win a Nobel in 1908. Next came Physiological Society Honorary Membership Food and Agriculture Organization. Strictly who shared the 1936 Prize with offer (‘What’s that?’) than just lay back and speaking, he was no longer a Member of The Henry Dale for their work on elucidating accept all accolades’ (Jonathan Ashmore, Society, having resigned just a few months chemical neurotransmission; the Argentinian President of Council, 2012–2014, personal before being awarded the Prize, apparently ; the Swiss Walter Hess; communication). because his career was moving away from and in 1966, the American Peyton Rous. science. As he had been a Member for over Rous, then aged 87 and the oldest person Even after that 2003 decision, there have 30 years, and his physiological background to ever receive a Nobel Prize in Physiology been some strange inconsistencies: the contributed much to his Nobel-winning of Medicine, had been an Honorary Member expression ‘four scientists’ suggests the four work, I consider he is rightly included in for 22 years. His win came 3 years after that living British Nobel laureates: , John this category. of his son-in-law Alan Hodgkin and 40 years Sulston, and ; and after his first nomination. indeed the first three were all elected that Tsien, like Neher and Sakmann, was an year. For some reason, not yet elucidated, ‘Affiliate’, a class of Ordinary membership Nobel laureates who became Hunt did not join their ranks until 2009. for foreign physiologists. Throughout the Members of The Society Certainly, some recent non-physiological history of The Society, there have been laureates have seemed somewhat bemused several types of membership available, but In recent years, Nobel prizes in Physiology to receive such an invitation, as Sir John from the very beginning, in 1876, there has or Medicine have frequently been awarded Sulston’s reply indicates. Refreshingly he been a category of Honorary membership, in areas far removed from ‘traditional’ admits he will ’break all records for inactivity for distinguished service to The Society or physiology, and recognising this, The as a member’ (Fig. 1). the subject. Strangely, especially in light of Society’s Executive Committee agreed in modern practice, some laureates became May 2003 to award Honorary membership Intriguingly, I have come across one early Honorary Members many years after their to those not already members, noting ‘there nomination of a ‘non-physiological’ Nobel awards; and more surprisingly, not all the are currently four scientists who should laureate, the geneticist TH Morgan (NP 1933). Members listed in Table 1 were offered receive this honour‘. Since then, most British In 1936, the Committee decided to offer him the accolade. Perhaps the most glaring laureates (but not all), and several of the Honorary membership, but he appears not exception is that of Sir Frederick Gowland more physiological foreign laureates (but not to have been elected, and as yet I have been Hopkins, elected in 1892, knighted in 1925, all) have routinely been offered Honorary unable to ascertain what happened. There the recipient of the Royal and Copley medals membership. The practice of awarding may well be similar examples in the records of the Royal Society (1918 and 1926) and such honours to foreign physiologists does, awaiting discovery. Seeking information its President 1930–1935. Hopkins was however, have a longer history and goes back about more recent practice I contacted co-Nobel winner in 1929 for his discovery over 100 years. previous chairmen, one of whom recalled:

46 Physiology News / Summer 2017 / Issue 107 Table 2. Honorary Members who received the Nobel Prize

Year Prize Winner Hon. Member

1908 PoM Paul Ehrlich (1854–1915) 1903

1936 PoM Otto Loewi (1873–1961) 1934 1947 PoM Bernardo Houssay (1887–1972) 1935 ‘I cannot remember any 1949 PoM Walter Hess (1881–1973) 1936 actually turning offers 1908 Chem Peyton Rous (1879–1970) 1936 down – but then these people are so shell- shocked that it is harder to decline a Physiological Society Honorary Membership offer than just lay back and accept all accolades’

Figure 1. Email from Sir to Professor Dafydd Walters. Physiological Society Archives

‘Re discussions on the committee in the entered in a Candidates’ book which was then period 1988–1994 regarding Honorary circulated at scientific meetings for other membership for Nobel laureates. I am pretty Members to sign in support, before being sure that this was in the context of people subjected to the annual ballot at an AGM. who were close to physiology and there was little or no discussion of winners of the It is not possible to determine when their Physiology or Medicine prize who were from names were entered, but from close more distant specialities. I don’t recall that we examination of the Candidate’s page for had any specific procedures – it was pretty Banting it is clear that he had already ad hoc with committee Members simply been proposed before his Nobel Prize was suggesting names of possible candidates... announced, by Lawrence Henderson of I cannot recall any specific examples! I Harvard, not by his then boss and co- certainly cannot recall anyone who refused laureate John Macleod (see Fig. 2). Banting’s us – I think I would remember that.’ nomination page is adjacent to that of (Graham Dockray, Committee Chairman another future Nobel laureate, Herbert 1991–1994, personal communication). Gasser (NP 1944). Otto Meyerhof’s situation is extremely curious (see Fig. 3). He was Finally, in this category there is an extremely nominated by AV Hill in 1930, 7 years after unusual group of just two Nobel laureates, they shared the Nobel Prize (modestly that both of whom became Ordinary Members of award is not recorded as a ’qualification’ on The Society after their Nobel Prizes. Neither the nomination form). As yet I can find no became Honorary Members. Both men, explanation for the timing of this nomination, Frederick Banting, the co-laureate with John 7 years after the Nobel Prize. This was not Macleod of the 1922 Prize, and the youngest the occasion when Meyerhof visited London winner of a PoM Prize, and Otto Meyerhof, to sign the Charter Book of the Royal co –laureate with AV Hill in 1923, were elected Society (he was elected FRS in 1937), nor in the then conventional way: proposed was it associated with his later flight from by a Member of The Society, their names Nazi Germany.

47 The questions surrounding Meyerhof’s election epitomise several of the curiosities and inconsistencies I have unearthed in trying to answer an apparently straightforward question. I have identified 61 Members of The Society who won Nobel Prizes, but in doing so have raised more questions about some of the individuals concerned, and about the role, strategies and activities of The Society. And I’m not entirely convinced that ‘61’ is the current definitive number. It is possible that even after intense scrutiny one or two names have slipped through the net, and I would welcome further comments or suggestions.

Acknowleldgements Many Members and staff of The Society have helped with the research for this article: Jonathan Ashmore, Jane Coppe, Graham Dockray, Casey Early, David Eisner, David Miller and Ann Silver. Unless otherwise noted, all information comes from records in The Society’s achives, held in the Wellcome Library, London. I would also like to thank Adam Wilkinson for assistance. I am supported by the Wellcome Trust. Figure 2. Candidates’ Book entries, on adjacent pages, for FG Banting and HS Gasser. The Physiological Society Archives

‘I’m not entirely convinced that ‘61’ is the current definitive number’

Figure 3. Candidates’ book entry for Otto Meyerhof. The Physiological Society Archives

48 Physiology News / Summer 2017 / Issue 107 Membership

Obituaries

parties, an annual childrens’ fun fair in the Olof was passionate both about his research cloisters and communal lunches before and his teaching. He particularly liked the fact lunch-hour lectures. Olof participated fully that in the ‘50s and ‘60s, if you wanted to do in everything. research then you had to be prepared to build your own equipment. He enjoyed doing that We wrote up papers together, with Joe while almost as much as carrying out the actual picnicking on Winterfold Hill, or on an island in experiments. His main research interests were the river at Walton-on-Thames, chaperoned in the areas of muscle units, tremor and by Olof’s parents. I loved that place, and when long-term changes in neural activity in the Olof told my husband Geoffrey and me in cerebral cortex following weak electrical 1970 that the hut next to his had become stimulation. This latter area has recently free, we moved with our three young children become at hot topic, and one of Olof’s papers into the holiday hut next door (no running from 1964 was remarkably cited more than water except for the river, no electricity then 50 times just this last year! Indeed, his work and no sanitation). on humans and animals from the 1960s has been more heavily cited these past 4 years Olof and I collaborated again in the late 1970s, than ever before. How many of us will have experimenting on pyramidal tract neurones that accolade? Olof enjoyed teaching both with Alex Milne, and writing a book on the medical and science students. He was often cerebral cortex. Meanwhile, the children were dissatisfied with the available textbooks and growing up; at the island Olof supervised my so sat down and wrote his own. Olof Conrad John Lippold tar papering of the leaking hut roof, advised our boys how to service the motor mower and He had, very importantly, a strong influence 1923 – 2016 build up the river bank, and of course we all on the recruitment of medical students at rowed, canoed and swam in the Thames. Olof UCL where he championed not only admitting In 1960, I started my PhD with Olof, studying was a wonderful mentor and friend to us all. more female students but also more people neuronal activity in the cerebral cortex of with non-standard backgrounds. anaesthetised rats. At that time he was Lynn Bindman sub-Dean and Tutor to the medical students Honorary Reader, Department of Olof retired from UCL and then became Head and I was struck by how very kind and patient Neuroscience, and Physiology, of Department of Physiology at Royal he was with them. He didn’t have an office University College London, UK Holloway College where he continued to separate from the lab, and I was experimenting research and teach. When he finally retired he behind a partition wall. Sometimes the medical built a lab in his own house and continued students had some serious things they wanted with his experiments. Indeed, he published his to discuss with Olof. One of the foreign last paper in 2000 and only stopped students was pregnant, far from her family, Olof Conrad John Lippold was born on 13 publishing when he could no longer afford the and the baby was illegitimate, a difficult February 1923 in London to a school master journal page charges. situation in those days. I was taken by Olof to father and a Swedish mother. Olof trained to visit her and the newborn baby, with a large be a medical doctor at University College Olof was very committed to his family. He parcel from Kay and himself as a gift. Hospital (UCH) during the Second World War, was married to his wife Kay, who he met as a when the preclinical medical school was nurse in UCH, for more than 60 years. He was It was also a revelation to me that neither evacuated to Leatherhead. The clinical training very proud of all of their six children and Olof, nor our part-time colleague Dr Joe at UCH remained in London, with bombs falling foster son, as well as their many grandchildren Redfearn, ever got cross or irritable with me nearby. Olof remembered in particular a V2 and great grandchildren. He loved to travel for when I did something stupid in the lab – landing next to Goodge St. station and being both work and pleasure. He had long-standing a useful life skill for me to learn. knee-deep in glass helping the wounded. He collaborations in the US, New Zealand and qualified in 1946, and did his army service as a Australia. For one sabbatical in New Zealand Although we were very serious about our regimental medical officer in the Royal he and Kay took several of their children and experiments and Physiological Society Engineers, then at the Army Operational travelled overland as far as India before flying activities, life at UCL was great fun in the Research Group, before returning to spend on to New Zealand. Their epic trek through 1960s and ‘70s. As well as sports at Shenley, most of his career working in the Physiology countries such as Iran and Afghanistan would there was time for staff/student Christmas Department at University College London. sadly not now be possible.

49 Olof was also a keen sportsman. He played In 2003, he joined the University of Nottingham Mike’s favourite mode of discussing research cricket and tennis at UCL and in later life took as Professor of Clinical Physiology, where he with his students was not to have meetings up swimming very seriously. He and Kay loved remained until his retirement in 2011; more but to come into the laboratory at the end of competing in Masters’ competitions all round recently, he taught at the Open University. each day and holler ‘what’s the answer?’ the world, often both winning gold medals. Many lived in the dread of this, until one Olof died peacefully on 7 December 2016, Mike’s lifelong research interest was in amino audacious customer piped back Bob Dylan’s aged 93. acid metabolism and transport particularly in words to him: ‘the answer my friend is blowing skeletal muscle. He was an early adopter of the in the wind’. A haughty Professor may have Richard Cogdell (Olof’s son-in-law) use of stable isotopes in man in conjunction taken offence at such impudence, but after Hooker Professor of Botany, with mass spectrometry to investigate being left momentarily speechless (perhaps for University of Glasgow, UK metabolism in health, exercise and disease. His the first time in his life), Mike cracked an research on muscle protein turnover, hormonal embarrassed grin followed by his signature changes during exercise and his early work on belly laugh. The refrain, however, was the effects of exercise on Duchenne muscular changed to ‘what new have you found today?’ dystrophy, sarcopenia and atrophy remain but failed to carry the same foreboding in significant landmarks in the field of muscle the questioned. physiology. At Nottingham, he applied these to muscle wasting conditions and the relationship Mike never appeared lithe despite cycling 4 of muscle wasting to ageing. miles every day from Invergowrie to Dundee, going for a run, regularly, during lunch time Mike was Head of the Physiology department (not a pretty picture upon return) and being a at Dundee from 1983 to 1988 and again keen hill walker. This was perhaps because the from 1991 to 1997, and also of the Division calorie burn was compensated with time of Biological Sciences from 1997 to 1998. spent in local watering holes located a short Despite obtaining a diploma in management, walk from the Physiology Department in the his management style was unconventional and Old Medical School building. An inebriated bet often abrupt; he later recognised a lack of with a rival laboratory about running up the nuance in his repertoire of professional Arthur’s Seat at the Edinburgh Physiological interactions as a missed virtue. However, the Society meeting was a consequence of this intention in the abruptness borne of frustration indulgence. The next morning the esteemed was always for the recipient to achieve Symers Professor of Physiology was seen excellence, realise potential with a relentless, lumbering half way up Arthur’s seat and then almost obsessive, pursuit of attention to detail. heaving over a boulder; arriving half an hour For postgraduate students this training was late for a conference session because, despite invaluable but others of senior vintage did not losing the bet badly, he had to complete the always see this approach as necessary or task. An enthusiastic participant in other productive. Mike was always one of the departmental social and sporting activities Michael John Rennie hardest-working staff members in the some will recall the vibrant departmental 1946 – 2017 department with a record to prove it: in terms Christmas parties, summer tennis outings or of receiving grant awards or publishing high- cricket matches when the sun shone in quality research papers, there were few in his Dundee. The work hard, play harder lifestyle Michael John Rennie, Symers Professor of department, or in the institutions where he was not without consequences, and it is Physiology at the University of Dundee, who worked, that could match his scientific output. difficult to judge what role this may have died aged 70 on 9 January 2017, was played in a relatively early demise. described by his colleagues and friends as a The undergraduate students approached force of nature, larger than life and a bit like Mike’s lectures and tutorials with Mike mentored over 25 postgraduate Marmite: you either liked him or you didn’t. His apprehension but enjoyed the intellectual and students and numerous postdoctoral fellows key character traits were loyalty, generosity, social engagement. One Red Nose day Mike (most pursued careers in research related to both intellectual and material, and how well he raised money for charity after being human physiology and remain indebted to his engaged with the non-academic staff in his challenged by the first year medical students contribution in initiating their careers) and department and throughout the University. to deliver his lecture wearing long johns and in published over 350 peer-reviewed articles. The technical staff and Jannies (janitors) boots filled with cold porridge after having A keen supporter of scientific societies referred to him simply as Mike (partly because half his moustache shaved on stage. (The Physiological Society, the American of his habit of working late and on weekends) Incidentally, he then changed into a suit and Physiological Society, European Society of and were readily offered any help whether for proceeded, nonchalantly, with only half a Parenteral and Enteral Nutrition, amongst professional or personal matters. moustache, for a meeting with the University others), he published many of his papers in Principal and other Heads of department. Society journals and also served on the Born in Newcastle upon Tyne, he was a proud editorial boards of numerous journals. Mike alumnus of The Royal Grammar School where Mike’s PhD and clinical MD students also was elected a Fellow of the Royal Society of he entered as an Ochiltree Scholar. Mike appreciated his style of mentorship that was Edinburgh in 1995. He was the GL Brown charted his scientific path from the non-officious and cultivated independence. prize lecturer (2004/2005) and served as Universities of Hull (BSc, Hons), Manchester Most of his PhD students would see him for the interim editor of The Journal of Physiology (MSc), Glasgow (PhD), Washington, St one-to-one meetings perhaps three times (2009–2010). Mike is survived by his wife Louis (MRC Travelling Fellow), University during their 3 years; this was partly due to Anne, daughters Louise and Eleanor, son College London (Lecturer and Wellcome extensive administrative duties as the Andrew and five grandchildren. Senior Lecturer) to Dundee where, at a Head of Department. This did not mean that relatively young age of 37 years, he was he did not take interest in one’s research Aamir Ahmed (PhD student 1987–1990) appointed as the Chair and 2 years later the or did not insist on a high quality of work Centre for Stem Cell and Regenerative Symers Professor of Physiology in 1985. both experimental and written, far from it. Medicine, King’ s College London, UK

50 Physiology News / Summer 2017 / Issue 107 While in medical school, he realised that he In 1998, Chandler joined forces with Stephen was not attracted to clinical practice but Hollingworth and Stephen Baylor in Baylor’s rather to the experiments that he carried out laboratory at the University of Pennsylvania in the basement laboratory of Warren Rehm, a to study ‘calcium sparks’ (a novel ECC calcium membrane transport physiologist. After signal first discovered in heart muscle cells medical school, Chandler worked at the and thought to reflect the coordinated release National Institutes of Health in the laboratory of calcium from a small number of SR release of KS Cole, an inventor of the voltage-clamp channels). These experiments and analyses technique. This was followed by a year-long revealed that, during a typical spark in a frog fellowship at Brown University, where he twitch fibre under physiological conditions, studied mathematical methods of science. He about 20,000 calcium ions are released in then moved with his family to Cambridge, about 4 ms, probably from 2–4 active England, for 3 years to work in the laboratory channels (16 oC). of Nobel laureate Sir Alan Hodgkin. During that time, he was involved in ground-breaking Knox had many notable non-scientific experiments on the electrical properties of interests, most related to family life with nerve axons (with Hans Meves) and of muscle Caroline, his wife of almost 60 years, their cells (with Hodgkin and Richard Adrian). The four children (Knox Jr, Janet, Cara, and Margi), muscle experiments employed the first use of and family travels to exotic places. They a three-micro-electrode technique that entertained generously at their home in North permitted measurements of currents across Guilford, CT, where friends – and friends of William Knox Chandler the surface and transverse-tubular friends – were always welcome. There, Knox 1933 – 2017 membranes of a muscle cell. This technique and Caroline pursued projects that included was then adapted at by home movies, an organic garden, restoration Chandler and Schneider to make the first of an historic barn, the creation of a pond in William Knox Chandler, an eminent American measurements of muscle charge movement. their back meadow, and, in collaboration with physiologist, died on 20 March 2017, at the In this work – indeed, in all of Chandler’s work the Guilford Land Trust, the preservation of age of 83 of a haemorrhagic stroke. He was a – a strong quantitative understanding was nearby land as open space. Knox’s Texas roots member of the Yale University Department of coupled with sophisticated experimental were often on display, including his fondness Physiology from 1966 until his retirement in techniques to unravel an important problem in for down-home barbecue and country music. 2010, and a leading figure in the fields of cell physiology. Knox also had a mischievous and unique sense nerve and muscle physiology. of humour, which combined the cerebral with In 1977, Chandler turned his attention from the ordinary, and included a wardrobe of Chandler’s work was recognised by his events on the exterior membranes of a T-shirts printed with ironic comments on life, election to the US National Academy of muscle cell to those within the cell’s interior, politics and the state of the world. Sciences in 1990. The citation described him i.e. to later steps in the ECC process. Chandler, as ‘the world’s leading investigator of with a number of co-workers, developed and In retirement, Knox returned to his first excitation-contraction coupling’ (ECC), also extended methods for using indicator dyes to passion and ‘read physics’, with a particular noting that he ‘opened new areas of research measure accurately the rise and fall of the interest in quantum phenomena. in the cellular physiology of nerve and muscle.’ cytoplasmic calcium concentration in a muscle His 1973 article (with Martin F Schneider) cell in response to membrane depolarisation. Stephen Baylor, reported the first measurement of muscle These signals serve to trigger muscle Department of Physiology, ‘charge movement’, a small non-linear contraction and relaxation, respectively. In the University of Pennsylvania, USA membrane current of a skeletal muscle cell 1990s, Chandler returned to the marking a voltage-dependent rearrangement measurement of muscle charge movement, of a protein known as the ‘dihydropyridine which by then was known to involve two receptor’, which serves as the voltage-sensor kinetic components (Q-beta and Q-gamma), of ECC. As suggested in that article, this the puzzle being which component was most protein rearrangement is an essential link in directly related to initiating the release of the chain of events that allows a muscle cell calcium ions from the sarcoplasmic reticulum to contract in response to an action potential (SR, the interior membrane compartment on its surface membrane. that is the source of the calcium that initiates muscle contraction). Chandler’s laboratory Chandler was born on 13 October 1933 in showed that there is a kinetic Chicago. His father was a faculty member in relationship between SR calcium release and the English Departments at Harvard University the charge-movement components. A key and Vanderbilt University prior to joining the finding was that, even in the virtual absence US government in the early 1940s as an of SR calcium release, a Q-gamma component intelligence analyst. Following his father’s could be clearly measured; hence this death during World War II, Knox (still a child) component was likely not caused by calcium moved with his mother and brother Colston to release but rather was essential in triggering Brownwood, Texas. At age 16, Knox graduated release. from Brownwood High School, where he showed exceptional promise in quantitative Knox’s scientific trainees at Yale all knew their subjects. He attended college at Washington good fortune in having him as their mentor. and Lee and then the University of Louisville, He set the example of how to do rigorous cell graduating in 1953 with a major in pre- physiology while having much enjoyment in medical sciences. He received the MD degree the process. from Louisville in 1959.

51 Mitochondria: Form and Function 14–15 September 2017 Mary Ward House, London, UK

Abstract submission closes Monday, 10 July This Topic Meeting explores recent developments in mitochondrial biology, developments in understanding fundamental biological processes, and the way that these impact on cell health and function.

Scientific Organisers Sean Davidson, University College London, UK Michael Duchen, University College London, UK Beatrice Fillipi, University of Leeds, UK Andy Philp, University of Birmingham, UK Confirmed speakers Francesca Amati, , Switzerland Robert Balaban, National Institutes of Health, USA Diego De Stefani, University of Padova, Italy Verónica Eisner, Catholic University of Chile, Chile Beatrice Filippi, University of Leeds, UK Ian Ganley, University of Dundee, UK Valentina Giorgio, University of Padova, Italy Josef Kittler, University College London, UK Viktor Korolchuk, Newcastle University, UK Nick Lane, University College London, UK Antonio Zorzano, IRB Barcelona, Spain

More information at www.physoc.org/mitochondriaformandfunction