Category Archives: Science History

Seeing Depth in the Brain – Part II

By Andrew Parker, Oxford University

Stereo vision may be one of the glories of nature, but what happens when it goes wrong? The loss of stereo vision typically occurs in cases where there has been a problem with eye coordination in early childhood. Developmental amblyopia, or lazy eye, can persist into adulthood. If untreated, this often leads to a squint, or a permanent misalignment of the left and right eyes. One eye’s input to the brain weakens and that eye may even lose its ability to excite the visual cortex. If the brain grows up during a critical, developmental period with uncoordinated input from the two eyes, binocular depth perception becomes impossible.

My lab’s work supports a growing tide of opinion that careful binocular training may prove to be the best form of orthoptics for improving the binocular coordination of the eyes. Recent treatment of amblyopia has tended to concentrate on covering the stronger eye with a patch to give the weaker eye more visual experience with the aim of strengthening the weaker eye’s connections to the visual cortex. Now we understand from basic research like ours that there is more to stereoscopic vision than the initial connection of left and right eyes into the primary visual cortex.

Ramon y Cajal

Figure 2: Ramon y Cajal’s secret stereo writing, see Text Box

Secret Stereo Writing. The great Spanish neuroanatomist Ramon y Cajal developed this technique for photographically sending a message in code. The method uses a stereo camera with two lenses and two photographic plates on a tripod at the left. Each lens focuses a slightly different image of the scene in front of the camera. The secret message is on plate B, whereas plate A contains a scrambled pattern of visual contours, which we term visual noise. The message is unreadable in each of the two photographic images taken separately because of the interfering visual noise. Each photograph would be sent with a different courier. When they arrive, viewing the pair of photos with a stereograph device as in Figure 1, the message is revealed because it stands out in stereo depth, distinct from the noisy background. Cajal did not take this seriously enough to write a proper publication on his idea: “my little game…is a puerile invention unworthy of publishing”. He could not guess that this technique would form the basis of a major research tool in modern visual neuroscience.

Our lab is investigating the fundamental structure of stereoscopic vision by recording signals from nerve cells in the brain’s visual cortex. One of the significant technical developments we use is the ability to record from lots of nerve cells simultaneously. Using this technique, I am excited to be starting a new phase of work that aims to identify exactly how the visual features that are imaged into the left eye are matched with similar features present in the right eye.

The neural pathways of the brain first bring this information together in the primary visual cortex. Remarkably there are some 30 additional cortical areas beyond the primary cortex, all in some way concerned with vision and most of them having a topographic map of the 2-D images arriving on the retinas of the eyes. The discovery of these visual areas started with Semir Zeki’s work in the macaque monkey’s visual cortex. Our work follows that line by recording electrical signals from the visual cortex of these animals. To achieve this, we are using brain implants in the macaques very similar to those being trialed for human neurosurgical use (where implants bypass broken nerves in the spinal cord to restore mobility).

turbot

Figure 3: A very odd form of binocular vision in the animal kingdom. The young turbot grows up with one eye on each side of the head like any other fish, but as adulthood is reached one eye migrates anatomically to join the other on the same side of the head. It is doubtful whether the adult turbot also acquires stereo vision. Human evolutionary history has brought our two eyes forward-facing, rather than lateral as in many mammals, enabling stereo vision.

My lab is currently interested in how information passes from one visual cortical area to another.  Nerve cells in the brain communicate with a temporal code, which uses the rate and timing of impulse-like events to signal the presence of different objects in our sensory world. When information passes from one area to another, the signals about depth get rearranged. The signals successively lose features that are unrelated to our perceptual experience and acquire new properties, corresponding closer to perceptual experience. So, these transformations eventually come to shape our perceptual experience.

In this phase of work, we are identifying previously unobserved properties of this transformation from one cortical area to another. We are examining how populations of nerve cells use coordinated signals to allow us to discriminate objects at different depths. We are testing the hypothesis that the variability of neural signals is a fundamental limit on how well the population of nerve cells can transmit reliable information about depth.

To be specific, we are currently following a line of enquiry inspired by theoretical analysis that identifies the shared variability between pairs of neurons (that is, the covariance of neural signals) as a critical limit on sensory discrimination. Pursuing this line is giving us new insights into why the brain has so many different visual areas and how these areas work together.

It is an exciting time. We still need to determine whether our perceptual experiences are in any sense localised to certain regions of the brain or represent the activity in particular groups of neurons. What are the differences between types of neural tissue in their ability to deliver conscious perception?

There are many opportunities created by the newer technologies of multiple, parallel recording of neural signals and the ability to intervene in neural signaling brought by the use of focal electrical stimulation and optogenetics. By tracking signals related to specific perceptual decisions through the myriad of cortical areas, we can begin to answer these questions. The prospect of applying these methods to core problems in the neuroscience of our perceptual experience is something to look forward to in the forthcoming years.

Seeing Depth in the Brain – Part I

By Andrew Parker, Oxford University

The Physiological Society set up the annual, travelling GL Brown Prize Lecture to stimulate an interest in the experimental aspects of physiology. With predecessors such as Colin Blakemore and Semir Zeki, following in their footsteps is a tall order. They are not only at the very top scientifically but also superb communicators.

My lecture series on stereo vision has already taken me around the UK, including London, Cardiff, and Sheffield. I’ll be at the University of Edinburgh on 15 November and Oxford University on 23 November. It’s a nice touch that GL Brown’s career took him around the country too, including Cambridge, Manchester, Mill Hill and central London, before he became Waynflete Professor in my own department in Oxford. The other pleasurable coincidence of giving lectures on stereo vision this year is that there is a 50th anniversary since fundamental discoveries were made about how the brain combines the information from the two eyes to provide us with a sense of depth.

In his 1997 book How the Mind Works Steven Pinker wrote, “Stereo vision is one of the glories of nature and a paradigm of how other parts of the mind might work.” I can’t claim to have written this inspiring sentence myself, but I can at least claim to have chosen stereo vision as my field well before Steven Pinker wrote his sentence.

Stereo vision is, in a nutshell, three-dimensional visual perception. It is the use of two eyes in coordination to give us a sense of depth: a pattern of 3-D relief or 3-D form that emerges out of 2-D images arriving at the left and right eyes. These images are captured by the light-sensitive surface of the eye called the retina. Stereo vision gives us the ability to derive information about how far away objects are, based solely on the relative positions of the object in the two eyes.

Victorian stereograph

Figure 1: “The stereograph as an educator,” illustrating the virtual reality technology of the Victorian era.

The Victorians amused themselves with stereo vision (see Figure 1). Virtual reality is our modern day version of this, but what comes next? The next generation will probably enjoy “augmented reality” rather than virtual reality. With augmented reality, extra computer-generated imagery is projected onto objects in the real world. The aim is to create a perceptual fusion of real objects with virtual imagery. For example, in one prototype I have seen, surgeons perform their operations with virtual imagery (acquired with diagnostic imaging devices) superimposed upon the surgical field in the operating theatre. Needless to say, this places much higher demands on the quality and stability of the virtual imaging systems.

What causes people like Pinker, who are outside the field, to get so excited about stereo vision? Partly it’s just the experience itself. If you’ve been to the 3-D movies or put on a virtual reality headset, you will have the sense of stereoscopic depth. It is vivid and immediate. The other thing that excites Pinker is the way in which the brain is able to create a sense of a third dimension in space out of what are fundamentally two flat images. As a scientific problem, this is fascinating.

We also see parallels between stereo vision and how other important functions of the brain are realised. One straightforward example of that is visual memory. Gaining a sense of stereoscopic depth from two images (left and right) requires matching of visual features from one image to another. Remembering whether or not we have seen something before requires matching of a present image to a memory trace of a previously seen image. Both processes require the nervous system to match visual information from one source to another.

Another aspect that Pinker is highlighting is the way in which the two flat images in stereo are fused to form with a new perceptual quality, binocular depth. A great deal of spatial perception works this way. One obvious example is our ability to use the two ears in combination to form an impression of sound localised in space, based just on the vibrations received by the left and right ear canals.

What is the world like without stereo vision? While you can partly experience this by placing an eyepatch over one eye (try playing a racket sport or carefully making a cup of tea), the difference is most strongly highlighted by the very rare cases when stereo vision appears to have been lost but is then recovered. Susan Barry, professor of neurobiology at Mount Holyoke College, was stereoblind in early life but eventually gained stereo vision with optometric vision therapy.

In a New Yorker article by Oliver Sacks (Stereo Sue, A Neurologist’s Notebook, June 19 2006) Barry describes her newly acquired perception of the world. “Every leaf seemed to stand out in its own little 3-D space. The leaves didn’t just overlap with each other as I used to see them. I could see the SPACE between the leaves. The same is true for twigs on tree, pebbles on the road, stones in a stone wall. Everything has more texture.”

Check back next Wednesday for Part II of Andrew Parker’s blog on stereo vision.

#LGBTSTEMDay: Celebrating the diversity of science

By Shaun O’Boyle, founder of House of STEM

Today is the first International Day of LGBT+ People in Science, Technology, Engineering and Maths, celebrating and encouraging diversity in science.

We do better science when our teams are made up of diverse people, with different perspectives, skills, and ideas. To achieve that diversity, however, we must first remove the roadblocks that are causing some minorities to remain underrepresented in science.

These roadblocks can arise early. A recent study by the Institution of Engineering and Technology (IET) found that 29% of LGBT+ young people choose to avoid a career in STEM because they fear discrimination. We know from research published in Science Advances that those who do enrol in STEM courses are more likely to drop out.

4249_lgbtstem-day-logo_f2a-1200.jpg

Of those who do pursue a career in science, more than 40% are not ‘out’ to their colleagues, and this is having a negative impact on their career prospects. Remaining ‘in the closet’ also takes its toll on a person’s mental health, as they spend every single day monitoring, policing, and editing what they say and do. In the United States, one third of ‘out’ physicists have been told to stay in the closet to continue their career, and half of Trans physicists have experienced harassment in academia. We therefore need to work on the environments LGBT+ scientists work in, to make them more supportive and welcoming.

Take fieldwork, for example. For a scientist, field work can be dangerous—collecting samples near active volcanoes, gathering data in areas of conflict, risking insect-borne diseases while documenting species in the rainforest—and so we prepare as best we can to minimise those risks.

When an LGBT+ scientist is invited to do field work, we must first make sure it’s not to one of the 72 countries where it’s illegal to be LGBT+, or one of the eight where our identity carries the death penalty. Even in countries with no legal barriers, we must make sure that we are not going to a region with a high incidence of hate crime. These are complex risks to minimise. For example, we must make a choice about “coming out” to our colleagues—whether it is better to have their support, or if telling them risks us being accidentally outed on the trip.

LGBT+ scientists and our allies are working to ensure no one struggles to be themselves at work—whether it’s fieldwork or lab work, teaching or studying. Research initiatives such as Queer in STEM and the LGBT+ physical sciences climate survey are doing what scientists do best: gathering data. By having a clearer understanding of the experiences of LGBT+ scientists across different disciplines, we can develop supportive policies, and create more inclusive environments. Initiatives such as LGBTSTEM and 500 Queer Scientists are improving the visibility of LGBT+ scientists, helping to create role models for others in their fields.

Visibility is at the heart of a new initiative to amplify the voices of LGBT+ scientists around the world. Today is #LGBTSTEMDay, the first ever International Day of LGBT+ People in Science, Technology, Engineering and Maths. The initiative is being led by an international collaboration between four groups—Pride in STEM, House of STEM, InterEngineering, and Out in STEM—and supported by more than 40 organisations, including CERN, EMBL, Wellcome, and The Physiological Society.

#LGBTSTEMDay will see live events and get-togethers happen at physical locations from Brazil to Scotland, Toronto to Switzerland. Primarily, however, it will be an online campaign, and an opportunity to highlight the powerful work already being done by people, groups and organisations all around the world to advance the inclusion of LGBT+ people in STEM. We hope you’ll join us in celebrating the diversity of science.

Shaun O’Boyle is a science communicator and producer with a degree in Physiology and a PhD in Developmental Biology. He is the founder of House of STEM, a network of LGBT+ people who work in STEM in Ireland, and one of the organisers of LGBTSTEMDay.

Sir Roger Bannister and Exercise Physiology

Bannister_publicdomain_600pxBy Mark Burnley, University of Kent, UK.

On Saturday March 3, 2018, Sir Roger Bannister, the first person to run a mile in under 4 minutes, passed away. His run on the Iffley track in Oxford in May 1954 was one of the defining athletic feats of the 20th century. In reading Bannister’s autobiography, however, it is striking just how much one man managed to pack into life, and how relatively little of it was concerned with athletic performance. He was an amateur athlete whose career pathway was already chosen, and that career was clinical medicine.

Sir Roger Bannister was a neurologist first and an athlete second. This goes some way to describing how good he was at neurology! He published 81 papers on the part of our nervous system that controls involuntary actions like breathing (called the autonomic nervous system). He also wrote and edited several texts on disease in this system.

Bannister’s investigations of the physiology of the respiratory system during exercise took place during a research scholarship in the University Oxford’s Laboratory of Physiology in 1951. It may surprise you to know that this had nothing to do with his interest in athletics. Bannister was instead interested in respiratory control, and exercise was merely a means of testing stress placed on this system. This work was published in The Journal of Physiology in 1954.

In this study, he explored the effect of oxygen levels on the movement of air in and out of the lungs (called ventilation), and on physical performance. To do this he had participants, including himself, run at constant speeds and breathe room air, with 33%, 66%, and 100% oxygen. At the time, the reason for the reduction in ventilation and improvement in physical performance when breathing oxygen-enriched gases was not clear.

roger_bannister_2.jpg

Roger Bannister in 2009. © Pruneau / Wikimedia Commons, via Wikimedia Commons

Each of Bannister’s four participants is identified by initials, which is of course not allowed now. We know of three for certain (Bannister and his supervisor, Dr Dan Cunningham, who co-authors the paper, as well as Norris McWhirter [N.D.McW]). The latter was able to run with relative ease breathing 66% oxygen, and only terminated the treadmill test because “he had a train to catch”!

Throughout the paper, Bannister seems to interpret his results as a clinician: the participant’s subjective experiences of the tests seem almost as important as the respiratory variables themselves. In light of the sometimes extreme volume of data modern laboratory technology can produce, we shouldn’t forget to ask participants in physiological research how it felt.

Physiological research requires interactions with people in other ways too. In his acknowledgements, Bannister thanks, among others, Prof. Claude Douglas for help and advice. Where would exercise physiology be without Douglas? Everybody stands on the shoulders of giants. Even other giants do.

Sir Roger Bannister was special because he was an ordinary man who produced an extraordinary life’s work: on the track, in the laboratory, as a patron and administrator in sport and sports medicine, and in his clinical practice. His humanity shone through in everything he did, and his The Journal of Physiology papers are no different. Thanks for everything, Sir Roger.

Wikipedia, women, and science

Every second, 6000 people across the world access Wikipedia. The opportunity to reach humans of the world is enormous. Perhaps unsurprisingly, many eminent scientists, especially eminent female scientists, don’t have pages!

Melissa Highton is on a mission to fix this. Her first step was bringing together a group of students and librarians for an Edit-a-thon to update the page of the first female students matriculated in the UK, who started studying medicine at the University of Edinburgh. They’re known as the Edinburgh Seven.

Not only do Edit-a-thons provide information for the world, the Edinburgh Seven serve as role models for current students studying medicine at the University of Edinburgh.

Melissa shines light on Wikipedia being skewed towards men, and also on structural inequalities that lead to so few women having pages. Women are often written out of history; they are the wives of famous someones who get recognised instead, they get lost in records because they change their last name, or they juggle raising a family, meaning they don’t work for as long or publish as much.

Slide01

Having a forum to talk openly and transparently about these inequalities is one of the steps to closing the gap. Our event for Physiology Friday 2017 did just that, and we hope participants will continue the conversation. Listen to Melissa’s talk here.

 

Tales of a Nazi-fighting Nobel Prize winner

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

Plaque

The Blue Plaque. Photo credit: David Miller

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

AVHill

AV Hill in 1955. Photo credit: Harold Lewis

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

IMG_3700

A.V. Hill’s Nobel Prize certificate

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

House

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

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

Prize Lecture Memoria – Edward Sharpey-Schafer

M0020242 Portrait of Sir E.A. Sharpey-Schafer

Sir Edward Albert Sharpey-Schafer (1850 –1935) was an English physiologist and Fellow of the Royal Society. Born Edward Schäfer, he studied under the physiologist William Sharpey and became the first Sharpey Scholar in 1873 at University College London (UCL). In 1874 he was appointed Assistant Professor of Practical Physiology at UCL where he went on to become Jodrell Professor. He was elected a Fellow of the Royal Society in 1878 at the age of just 28. Schäfer was appointed Chair of Physiology at the University of Edinburgh in 1899 where he would stay until his retirement. He was one of the nineteen founder members of the Physiological Society in 1876 and he also founded and edited [the Quarterly Journal of] Experimental Physiology from 1908 until 1933. Schäfer was knighted in 1913. He is renowned for his invention of the prone-pressure method or Schäfer method of artificial respiration. He was very active as a facilitator, mentor, coordinator, teacher and organiser through much of his career. He had started as a histologist and always emphasised the importance of structural knowledge. He was the co-discoverer (in 1894, with George Oliver) of adrenaline (as in the adrenal-derived, circulating hormone) and he coined the term ‘endocrine’ as the generic term for such secretions. He intuited (as did a few others, independently) that insulin must exist (i.e. a pancreatic hormone to account for diabetes mellitus) and coined the name (originally as ‘insuline’). (Banting and Best actually discovered what S-S and the others had predicted). Thus, he had a founding role in modern endocrinology. He also did important early work on the localisation of function (e.g. motor centres) to brain regions. After the death of his eldest son, John Sharpey Schafer, and in memory of his late professor William Sharpey, he changed his surname to Sharpey-Schafer in 1918. Sir Edward Albert Sharpey-Schafer died on 29 March 1935 aged 84. Funded by bequests from Sir Edward Sharpey-Schafer (1850–1935) and his daughter Miss GM Sharpey-Schafer and in memory of Sir Edward and his grandson Professor EP Sharpey-Schafer, The Physiological Society established the Sharpey-Schafer Prize Lecture. This is a triennial lecture given alternately by an established physiologist (preferably but not necessarily from abroad) and a young physiologist chosen by The Society.