Francis McGlone

Francis obtained his BSc (Hons) in Neurobiology and his PhD in Neuroscience from the University of Sussex, UK. Whilst at Manchester University he investigated the roles of sensation in the neural control of movement, and subsequently the effects of hypnotic drugs on visual sensory and cognitive function – employing behavioural and electrophysiological techniques (EEG).  He took up the position of Senior Neuroscientist at the multidisciplinary Pain Research Institute (Dept. of Medicine, Liverpool University) in 1987 to carry out research into mechanisms of chronic neuropathic pain, using psychophysical, electrophysiological and neuropsychological approaches. This research included working with neurologists and neurosurgeons, developing intra-operative recording techniques for use during neurosurgical procedures on chronic pain patients, as well as a range of neurosensory testing procedures.

He moved to industry in 1994 (Unilever R&D) and as Lead Neuroscientist established a new research-base in Cognitive Neuroscience, exploiting the experiences he had gained at the Pain Research Institute.  Pain research demands a multidisciplinary and converging methodologies approach – from molecular neurobiology to belief systems – and as such recognises no single discipline in Medicine or the Life Sciences.  Its study demonstrates the power, and fundamental necessity, of interdisciplinarity in understanding the neural control of behaviour by addressing mechanisms of sensation, perception, behaviour, memory, emotion, neural plasticity, and the integrative aspects of nervous system function.  His goal was to bring a systems-approach to the study of the neurosensory, perceptual, cognitive and affective processes that underpinned the three ubiquitous human behaviours that sustained this FMCG company’s business – grooming, feeding and foraging (shopping).  These behaviours, being largely driven by low-level, homeostatic, and implicit (automatic) processes, rely upon physiological drivers, multisensory inputs, and are intimately connected with neural mechanisms of homeostasis and reward.  The focus shifted from understanding mechanisms of human pain, to understanding mechanisms of human pleasure. The science base was initially funded from a special Exploratory Research Fund, provided specifically for growing new science areas within R&D and that – importantly – was not allied to any short term business needs, and as such provided an opportunity to think big and to think long.   As a new science-base was being built, one in which by definition there was limited internal resource (staff or know-how), its operation depended on identifying, establishing, and funding, a global network of academic research collaborations, not only to bring the highest level of scientific support to address the often complex neurobiological and behavioural drivers of the aforementioned human behaviours, but as importantly to rally and coordinate the diverse skills required to tackle them.  This reliance on ‘orchestrating’ across different research disciplines in the pursuit of a common goal further reinforced the power of convergence in complex research areas such as the brain adn behavioural sciences.  The translational value of the research was exploited by product categories that had traditionally relied on research skills in Physical & Material Science and Chemistry, recognising that all of their products were used in the same basic human behaviours – feeding and grooming – and as such shared a common ‘substrate’. An example of how this model operated was provided by research carried out over a period of 10 years into mechanisms of itch and skin irritation, where product chemistry could, in some sub-populations, causes adverse skin reactions.  Understanding why is of critical importance to any cosmetic/body-care industry.

Researching preclinical conditions such as skin irritation led to the development and discovery of more sensitive diagnostic tools and a deeper understanding of a neuroinflammatory process.  Itch, like pain, is mediated by c-fibres and in chronic conditions causes severe psychological distress.  Its study is compounded by it having a strong psychogenic element – talking about it causes it to be experienced.  A number of research methods were used/developed including; iontophoresis to deliver histamine through the skin to induce itch and its associated neurogenic inflammation; laser Doppler instrumentation to quantify local blood flow changes; the development of intradermal microdialysis techniques to sample the pro-inflammatory mediators released by histamine in situ, or other mast cell degranulating molecules; subsequent tissue fluid analysis procedures e.g. MS, Q-TOF, MALDI to measure mediators such as SP or CGRP;  fMRI to study brain responses to iontophoretic delivery of histamine; the development of an ‘itch questionnaire’ modelled on the McGill Pain Questionnaire.  As grooming products are applied on many different body sites the above procedures were applied in the scalp skin, the axilla, and the forearm.  Each of these sites was also mapped psychophysically with Quantitative Sensory Testing (QST) techniques.  And each of these sites was found to have its own physiology and reactivity to itch induction.

The main collaboration for the fMRI neuroimaging studies was at Nottingham University where the group developed the first – and still only – human single-unit electrophysiology / fMRI recording capability.  As well as developing techniques in skin neurobiology and psychophysics, an early reliance was established on fMRI, and here pioneered the application of this technique (and other neuroimaging modalities) within the industry.  Much of the research also required the development of a wide range of bespoke instrumentation and software, especially for psychophysical and neuroimaging applications, and here again novel techniques and procedures were developed, such as direct single nerve electrical microstimulation during concurrent fMRI to map the cortical representation of low threshold mechanoreceptors, and the development of MRI compatible piezoelectric vibrotactile stimulators for studies on the sense of touch. One development – the requirement for synchronous recording of neuroelectric and haemodynamic signals from the brain to resolve cortical dynamics in somatosensory cortex – was successfully pitched to a venture capital group (Unilever Ventures) and secured, over a period of 4 years, an investment of $8M.  The objective was to market a medical device for use initially in pre-surgical mapping for epilepsy, and for basic neuroscience applications.

The sensory system at the core of his research interest is somatosensation – the body senses. The Sense of Touch (used here to include all of its sub-modalities – touch, temperature, pain/itch) is now recognised as also playing a role in affective, affiliative and social aspects of human social communication, and here his research provided a significant scientific contribution to the taxonomy of cutaneous c-fibres, with the characterisation of a population of c-fibres that are not nociceptors or puriceptors, but respond optimally to low force and velocity mechanical (stroking/caressing) stimulation, inducing a state of pleasure – hedonoceptors.   The description of the functional role of these c-fibre afferent nerves (called c-tactile afferents – CT) is still in its genesis, and the working hypothesis is that they code for the pleasant aspects of affiliative and social touch, in parallel with the role of c-nociceptors that code for pain. In collaboration, primarily with Gothenburg University and the University of North Carolina, he has advanced knowledge of the role of this sensory system in human affiliative and grooming behaviour. The current focus is on developing an animal (mouse) ex-vivo skin-nerve preparation to complement the use of direct single-unit nerve recordings in human subjects (the technique of microneurography), and in identifying the mechanosensory transduction mechanisms of CT-afferents.

One overriding ambition that has driven Francis’s research is its translational value – how does it relate to ‘normal’ human behaviours such as those that form the basis of many FMCG companies, and how does this sensory modality interact with other sensory modalities in an ecologically relevant and meaningful way?  There are also opportunities to exploit learning’s from this research into clinical arenas, such as pain and itch, as well as a number of neuropsychological and psychiatric conditions, but also into broader aspects of mental and social health and well-being, founded on understanding of the role of the brain in controlling the homeostatic and affective mechanisms that regulate behaviour.

Neurotechnology is predicted to be a trillion dollar enterprise and there are many opportunities to translate knowledge from basic neuroscientific research into areas of clinical and commercial benefit.

Francis is a firm believer in the power of collaborative and interdisciplinary research, and is also aware of the value of attracting media attention to research  - evidenced by press coverage from a talk delivered at the BA Festival of Science in Liverpool in 2008, a Nature Neuroscience publication of pleasant touch in 2009, previous TV and radio activities, and his work with the chef Heston Blumenthal.