What makes for keeping bones healthy?
Dr Paramabandhu Groves
Mindfulness: research and practice: how we know it works
What is mindfulness? It is a translation of ‘sati’ – awareness, paying attention moment by moment, intentionally and with compassion. In the 1970’s mindfulness was demonstrated to reduce pain and stress by two thirds, to increase self respect and empathy, and to raise the immune system (Full Catastrophic Living by Jon Kanat Zinn). This effect continued even after 4 years and even if people practised in a less formalised way. Further studies showed similar results in managing depression using mindfulness combined with Cognitive Behavioural Therapy. Particularly since 2010 and the publication of the government report, Mindful Nation UK, mindfulness has been promoted as improving mental and physical health and has been rolled out in primary and secondary care.
Key aspects of mindfulness:
1 : Stopping, or coming to ourselves
2 : Increasing awareness
3 : Moving attention around as we choose, for example from oneself to others, from the brain to the body, to different areas of the body
4 : Changing relationship to the content of experience: being present.
Your body IS. IS your mind? Becoming more aware of our present thoughts and the feelings attached to them, we can break dysfunctional habits and patterns. Much of the time we are on automatic pilot. If that automatic pilot tends to negative and resentful rather than positive thoughts, our well being will be eroded, leading to catastrophic thinking. Mindfulness provides a pause to enable us to connect, observe our thoughts, and become aware.
Body scanning or moving the attention round the body is a mindfulness technique enabling us to observe our thoughts, let them go and pull attention back to bodily sensations. The mind’s job is to think and pay attention to every detail. Body scanning trains us to be more present, not to think so much and to break out of the automatic pilot avoiding a lot of avoidable suffering.
Mindfulness or compassion based therapy enables us to accept even painful experience rather than drowning in it, or blocking it. We turn towards the experience, being interested in where emotions and sensations are located in the body and how these change as we hold them with kindness. This is counterintuitive since the natural reaction is to block, feel blame, be upset or angry. CBT and mindfulness takes the client straight to experiencing the thought and to recognise that thoughts are not facts. They are like buses which should be allowed to pass until you find one you want to catch. Feelings want to be felt, feel them with awaresness but don’t get stuck.
Be able to be solitary without being lonely.
Dr Fiona Watt
What is a stem cell? Stem cell theories and their applications. Stem cells and society
The origins of stem cell research lie in pathology and also In Vitro Fertilisation. Stem cells are the mother cells of all bodily tissues. They are found throughout the body. They reproduce themselves and they differentiate to form different tissues ie stem cell in the skin differentiate into skin. Embryonic stem cells are pluripotent, i.e. they can differentiate as necessary to create a whole foetus. Adult stem cells, on the other hand, have until recently been capable of reproducing only their source tissues. It is illegal to use embryonic stem cells either therapeutically or for research. Also there is a cancer risk associated with embryonic stem cells because they reproduce so quickly and can overgrow. Stem cells are now taken either from donated placentas or from donors own tissues. Originally, stem cells were taken from the tissues of the body to treat the source tissues. Cultured epidermis stem cells could produce keratinocytes capable of repairing the skin replacing skin grafts; neural stem cells could treat spinal injuries, corneal stem cells could treat corneal lesions. In the mid 2000s, however, Dr Yamanata discovered how to convert adult stem cells into autologous pluripotent stem cells (induced pluripotent stem cells or IPSs). These are capable of reproducing a range of tissues, not simply their source tissues, without being rejected by the body. This makes it possible to use them therapeutically to repair a range of tissues in the body. Stem cells are taken from fat, blood or bone marrow, and engineered to create IPSs. These can be used therapeutically to repair tissues. Most commonly stem cells are taken from fat, a procedure which less invasive than taking them from bone marrow.
Recent and future advances: a revolution in medicine
Stem cells have been cultured to create tiny organs or organoids in vitro. Gut lesions in mice have been repaired using organoids but so far this as not been applied to humans. Research on techniques for growing stem cells on scaffolds may enable the growth of whole organs rather than organoids. Recent research in combining IPS with gene therapy is working towards improving existing medical interventions. Combining immunotherapy with stem cells will enable immunotherapy to be more effective in treating cancer. Disease modelling, using tissues grown in vitro will enable drugs to be screened to identify the right one at the right dose for the individual patient. Growing human tissues in vitro from IPSs will also reduce using animals in medical experiments. An initiative is looking at the genetic basis for illness using IPSs from 700 donors. For example one twin may develop an illness which the other identical twin does not. The research is searching for the reasons for the difference. Research on stimulating the body to secrete or activate its own stem cells is underway in several institutes.
The MRC recently invested £100m in research which is hoped to yield £2b in medical advances. The main hurdles to translating stem cell research into practice are cost, risk averseness, and concern over ethical issues. Stem cell treatment for several health conditions is being promoted more in the US and eastern Europe than in the UK. These countries are less risk averse than the UK. Health tourism is growing in these areas. There are risks associated with having procedures undertaken in countries outside our regulatory system. A member of the audience gave her experience of travelling to Belgrade in Serbia for stem cell treatment for hip arthritis. This had resulted in eliminating arthritis in one hip and dramatically improving it in the other. She is returning for a repeat treatment for the hip which still has some arthritis with the expectation that the repeat treatment will further improve the hip.
Dr Vic Chapman : Eating Disorders: More than just a Diet
The incidence of eating disorders in the under-18 population is increasing, and Anorexia Nervosa is known to have the highest mortality of all psychiatric disorders. Eating disorders demonstrate a complex interplay between physical and psychological symptoms and are not only notoriously difficult to treat but cause a significant impact on young people – male as well as female – at a crucial stage of life. In this talk Dr Chapman considered the development of the illness and current research and views on treatment and management. Unlike the majority of serious illnesses, the inclusion of the family in treatment is critical to a productive treatment.
Dr Vic Chapman Consultant Child and Adolescent Psychiatrist specialising in eating disorders CAMHS, Royal Free Hospital.
Ann Blandford : Farewell to the GP – is Artificial Intelligence Going to Replace Doctors
This was an interactive seminar. Professor Blandford started by defining the role of a doctor: diagnosis, monitoring patients’ health, motivating people to live healthily, triage and so on. On the basis of the audience suggestions that she invited, she went on to contrast ‘real’ intelligence with Artificial Intelligence (AI). Real intelligence is things such as: acquiring knowledge, problem solving, improvising, collecting and remembering information, judgment, seeing patterns. AI does the cognitive things we humans don’t know how to do properly. While AI is useful to us it cannot necessarily mimic real intelligence.
‘Old fashioned’ AI is organized around human readable rules and based on the manipulation of symbols or representations. The latest developments in AI rely on algorithms, neural network models, ‘deep’ machine learning, which cannot be checked by humans so easily. Deep learning is based on neural networks with many hidden computational layers between inputs and outputs. They can be applied to massive data sets from which the neural algorithms can identify patterns and make subtle discriminations which humans would not always be able to achieve.
AI in healthcare
In the 1970s an expert system called MYCIN was created which aimed to replace human medical diagnosis. It was widely copied but the success of this approach was limited, and later went into abeyance. In the 1990s an AI-based decision support system was developed to support doctors but it could not replicate doctors’ reasoning. In the last decade new systems have appeared from companies such as DeepMind, using newly developed neural deep learning systems which have enabled exponential growth in computing processing and data storage. They are based on the digital health cycle: huge data sets are generated at the surgery and other usage points. The data fed into the system enables patterns to be identified.
DeepMind developed a system which was trained to recognize health problems by examining over 14,000 patient scans taken from the Royal Free Hospital. The Royal Free broke data confidentiality by sharing patient data with DeepMind without first gaining patients’ agreement, and the partnership was abandoned. Moorfields uses a DeepMind system to identify abnormal retinal scans. The system has been shown to perform as well as doctors.
Professor Blandford asked the audience how confident they would feel in machine diagnosis rather than diagnosis by a doctor. The audience expressed some concerns over trusting a computer rather than a doctor but recognised that computers might perform routine tasks better. Given AI’s relative accuracy AI is cost saving: doctors are more likely to over-refer, rather than under-refer, out of concern to eliminate possible health problems. This creates a longer waiting list for specialist services than might be necessary.However, computers deal with structural disease rather than functional disease, and cannot take a holistic approach to the patient. Also doctors deal with ambiguity whereas computers deal with ‘what is’ rather than ‘what might be’. AI systems are subject to accretion bias. Layers upon layers of data and decision may tend to confirm patterns and not allow for eccentric cases.
Babylon is an online system which is now open to the public as a digital GP. Patients have to deregister from their GP. It has the advantage of being convenient, cost effective, consistent, reliable and scalable. It is claimed that Babylon beats humans doctors in diagnosis. However the quality of the diagnoses are criticized. Babyon deals poorly with complexity. It tends to be used by younger people with less complex conditions. Babylon appears to be taking the easier cases and leaving the more complex and chronic cases for GPs to deal with. GPs are increasingly overloaded and pressured. Also patient confidentiality is at risk. It is not clear who owns patient data since data sharing is how the system learns.
Looking to the future, will we better understand what types of problems are tractable? The case of autonomous vehicles suggests we should be cautious. AI systems are effective in dealing with simple problems requiring consistent responses, but cannot easily be “hands on”. Doctors have the skill of understanding the type of person who has the disease as well as the disease itself.
Dr Isabelle Bloomfield : Learning how to keep brain cells healthy- my experience at the Francis Crick Institute
The Francis Crick Institute was set up in 2016, bringing leading university and research centres into a ‘cathedral of science’. The Institute aims to encourage interdisciplinary collaboration and breaking down barriers. The building is conceived around an open space with crossing walkways to facilitate synchronistic meetings. The Crick Institute’s mission is to make discoveries in the biology of human health and disease. The focus is on: cancer, the immune system, growth and development, health and ageing, and infectious diseases. The Crick prioritises translating science into treatment. In 2013, Dr Blomfeld started her postgraduate research into brain development and growth, at the National Institute for Health Research (NIHR). In 2016 the NIHR moved into the Crick Institute and Dr Blomfeld moved with it into the Guillemot laboratory. In 2018 she received her PhD and started post-doctoral research. This was an unlikely career for a child who grew up without any science background in the family, and who loved the arts as much as the sciences. Her childhood interest in human biology was sparked by a love of animals and nature. Blomfeld’s research is into neural stem cells (NSCs). Neurons are the cells in the brain and nervous system which have thoughts and judgments, store and manage information, send messages, and so on. Stem cells are the original ‘mother cells’ which differentiate and develop into the different bodily tissues, including nervous and brain tissue. Blomfeld’s specific research is into how NSCs form, develop and respond to signals. She is working to understand how the NSCs identify loci where they are needed throughout the neural tissues, enabling continuous brain regeneration. How is it that quiescent NSCs wake up and become active, creating new neural cells? They seem to be waiting and listening for a mystery signal, which switches them on. Blomfeld is part of team looking at the molecular mechanism within the NSC. In vitro, DNA is forced into an NSC, which, following a mystery signal, creates a protein which develops into the new cell. She is concerned with what switches the NSC on and off, enabling it to develop and differentiate into neural cells and to find its way to the places it is needed. How is this process regulated? The brain needs to produce new cells to create new knowledge, and stay adaptable and plastic. However, it is not beneficial to create too many new brain cells since the new cells can override old knowledge. Also NSCs can become exhausted by overstimulation. Damaged NSCs can overgrow and create cancer.NSCs have been found mainly in the hippocampus ( the seat of memory) although they are also found in the lateral ventricles. When they die off the brain cannot regenerate, and depression and Alzheimers follow. In the past it was held that the adult brain cannot create new neurons (neurogenesis); that, once adult, one has all the neural cells one will ever possess. However, recent findings have shown that the brain does create new neurons throughout life although neurogenesis may slow down as we age. NSCs were found in mice in the early 1960’s, in birds in 1980s, and in humans and fish in the 1990s. In 2018/9 researchers claim that the adult human brain contains NSCs and that they are capable of creating new neurons. Whether this is neurogenesis or the wakening up of existing cells, or indeed, merely the creation of new neural pathways, is controversial. If Dr Blomfeld were to identify the mystery signal which wakes up existing NSCs we would be able to regenerate the brain. Translating this research into therapy for degenerative neurological illnesses, such as Parkinsons or Huntingdon’s Disease is a long way off, however. Simply putting new NSCs in the brain would not be effective. It is necessary to transplant the NSC with the DNA to create protein, and to be able to switch NSCs on and off. Also the old neural pathways would be destroyed between the replacement neurons and existing ones. Our ability to study how the brain works is limited since we cannot examine a whole living brain. We have to work with slices of the brain. Recent discoveries are, nevertheless, exciting. Astracytes can act as NSCs in strokes, enabling the part of the brain affected to regenerate. Orgonoids taken from NSCs can be spun in a dish. They then start making structures. Neurogenesis is very sensitive to overall bodily health and the environment or surrounding tissues in which the stem cells are embedded. A diet rich in antioxidants, folic acid, B12 and omega 3 appears to be beneficial. Exercise increases blood flow to the brain and grows new blood capillaries. Learning and social interaction create new neural pathways. Stress inhibits the creation of new neural pathways. However we do not yet know if these factors improve the functioning of existing cells or whether they also facilitate neurogenesis. The mechanism for this effect is not yet clear.
Dr Perlmutter’s Brain Maker: the power of gut microbes to heal and protect the brain
Dr Isabelle Blomfield of the Francis Crick Institute for Medical Science introduced a film of a discussion by Dr Perlmutter and Dr Bredesen of the Buck Institute of Research into Ageing. She pointed out that the research it refers to, into the impact of diet nutrition and lifestyle on brain health, is considered controversial in mainstream neuroscience. The film is part of a series by Dr Perlmutter a distinguished neuroscientist based at the Buck Institute in California. Dr Perlmutter and his colleagues practise Functional Medicine, 21st century, personalized medicine relying on the full range of medical and non-medical interventions to ameliorate disease. As well as relying on orthodox medicine, functional doctors use nutrition, diet, supplementation, herbs and homeopathy.Dr Perlmutter explained that there is little funding for research on how nutrition and diet could affect the onset and progress of chronic degenerative disease like Alzheimer’s. Research has concentrated on cellular biology and genes. By far the greatest funding goes to big pharma which tend to identify a single disease cause or trigger, and single drug to treat it. Alzheimer’s, for example, is seen as due to low levels of acetycholine in the brain, the chosen drug increases acetycholine levels. However this drug is of limited effectiveness since Alzheimer’s is caused by multiple factors not a single one. Dr Perlmutter’s research is into the effect on the brain of lifestyle, nutrition and diet. He shows that the microbiome, which is largely in the gut, affects brain health and can mediate the progress of conditions such as Alzheimer’s and autism. Over the last 5 years research into the microbiome has shown that gut health determines overall health in subtle ways. 99% of our DNA is in the gut biome; only 1% is from our parents. So we can affect the progress of brain conditions like Alzheimer’s and autism by cherishing our gut biome. A clinical experiment showed that 90% of Alzheimer’s patients experienced improvement on a low carb diet, maximal Vitamin D supplementation (up to 85/90) and exercise. Autism has been shown to be related to dysbiosis. A ketogenic diet has been shown to reduce the expression of the Alzheimer’s gene.
Research by the Buck Institute into preventative neurology screens all drugs to identify those which might trigger or worsen dementia. The research showed that statins may be causally linked to Alzheimers and other dementias. Fats are essential to brain function and cognition. Statins interrupt the CQ10 pathway leading to low energy and impaired cognition. Low cholesterol appears to be linked to Alzheimer’s. Dr Bredesen says that thanks in large part to a dramatic new understanding of the brain/gut connection there is new hope for the treatment of autism to Alzheimer’s to multiple sclerosis. The film describes many cases treated by Dr Perlmutter which responded very well to improvements in the gut biome.
Dr Isabelle Blomfield commented on the Buck Institute’s research. There is no proof that nutrition, supplementation and lifestyle can affect the progress of dementia. However, she agreed that a healthy lifestyle and balanced diet will benefit the whole body.
Professor Irene Leigh : What happens when genes go wrong in the skin
Professor Leigh’s research has focused on genetic skin disorders. There are over 2000 skin conditions. The big advantage of skin as an organ is that you can see it. She became interested in genetic skin disease as a consultant at the London Hospital and set up a clinic to diagnosis and treat diseases. Professor Leigh started by presenting a basic outline of the human genome. The human genome has 3300 million bits of information in each cell’s DNA. A large paperback book contains about 100,000 bits, so to read the number of bits in the genome you would need to read a book a day for 100 years. She then talked about advances in understanding the genetic basis of certain skin diseases. The skin’s functions include physical protection, acting as a barrier to keep the inside in and outside out, temperature control, and so on. Genetic skin diseases include: an inadequate horny outer layer formation, skin weakness or fragility, cancer, and the separation of the skin’s layers. Genes in the skin go wrong due to mutations in germ cells (germline mutations) or mutations in other cells (somatic mutations). Germline mutations result in proteins not being manufactured, or the wrong ones being produced. Looking for a defective gene is like looking for a needle in a haystack. Genetic abnormalities are passed on either by dominant or recessive transmission. Dominant disorders are caused by 1 normal and 1 mutated copy of a gene leading to a 50 – 50 chance of a person inheriting the disorder. Recessive disorders are caused by 2 copies of a defective gene – one from each parent. The condition may or may not remain dormant and the child may or may not suffer the illness. Recessive genes are commonest in societies with strong consanguinity (interbreeding). Recently, new technologies have been developed to identify defective genes: automated sequencing and in silico cloning. 160 skin genetic disorders are now understood. Professor Leigh then discussed 2 representative examples of skin disorders, one recessive, one dominant. Recessive Dystrophic Epidemoloysis Bullosa (RDEB) is the separation of the epidermis, or outer skin layer from the dermis, or inner layer leading to blistering and scarring. It is a lifelong condition with a high cancer risk (see‘The Boy whose Skin Fell Off’). In 1983 a missing protein was identified in skin by new antibody LH7. RDEB is a deficiency in a Type VII collagen. There are 3 possible ways to correct the deficiency: gene therapy: replacing the gene; protein therapy inserting the missing protein; cell therapy inserting normal cells. Gene therapy involves tissue engineering, replacing defective skin with lab-cultured skin cells. This will increase the repaired skin from a postage stamp size to 2 metres squared in 2 weeks. It is life saving but costly. An alternative, vectorology, is inserting a new gene, using a virus (vectorology). Gene therapy leads the way for ex vivo gene therapy. The first RDEB patient was treated in 2005. Now the treatment is carried out in many centres, such as St Thomas’s. Other options, protein therapy and cell therapy are more difficult. Dominant: Keratin Filament Assembly is when defective genes interfere with Keratin assembly. An example is Pachyonychia Congenita. Prevalent among Mormon community in Utah, it is rare and is usually associated with thickened toenails, thickened skin on the bottom of the feet, and plantar pain. About 1 in 10 Europeans carry a mutation predisposing to this disease. Treatment: is to disrupt the gene transcription (normally using siRNA). A recent technique called CRISPr-CAS-9 is used. In 2013 Professor Leigh did a study of the incidence of non-melanoma skin cancer which showed that sun-exposed normal skin is already a “quilt” of cancer-causing mutations. She urged that prevention is better than cure.
Liz Sampson : What research is teaching us in order to meet the complex needs of frail older people at the end of their lives
Margot Waddell : Inside Lives
Psychotherapist and Cambridge educated classicist Margot Waddell’s theme was the understanding of the personality’s journeying through life’s stages particularly the later years of life. She continues to be fascinated by the relationship between psychological theories, our ‘inside lives’, wisdom and knowledge. Margot questioned the classical Freudian theory that different development stages are necessarily age specific: for example that the oedipal stage ends at about 6, or that adolescence ends in the teens. If unresolved issues remain, the different stages can reoccur throughout our lives: later life experiences can push you back into earlier unresolved stages. For example retirement can trigger issues you had leaving school: losing the carapace, your protective covering, and facing a new and unknown future without it. She noted that adolescence is characterized by a strong internal time scales, not congruent with external time. These different time scales needs to be appreciatedand allowed to take their course if adolescence is to be resolved. Demand for psychotherapy has risen by 50% over the last 5 years, and self-harm among young girls is at its highest ever level. These increases seems to have been caused by prevailing examination pressure, lack of self-esteem, anxiety and exhaustion. Adolescence may continue throughout life, as may infantile feelings of
abandonment, separation and loss.
Dr Marianna Fotaki : Turning fear into purpose: responses to the refugee communities and voluntary organisations in the Mediterranean
Marianna’s talk was based on her Doctoral thesis Lesbos, dreams and choices, arising from her two year project in the Greek islands. The project examined initiatives to help refugees: what motivates local communities and volunteers to set
up these initiatives, and how collective and individual histories might influence local responses to refugees’ needs. To understand how participants themselves interpretthese events, she combines oral stories of volunteer involvement in humanitarian activities, ethnographic research into locally organised responses to refugee arrivals, with macro-level historical analyses. Her overall aim is to learn from successful solutions to the logistical challenges, and tensions between refugees and local inhabitants, to guide present and future policies.
Dr David Zigmond GP : If you want good personal healthcare – see a vet
David’s session followed a question and answer format. It drew on his anthology If You Want Good Personal Healthcare – See a Vet examining major questions in modern medicine. In his session David outlined his experience and analysis of such complex concerns as: What kinds of human suffering constitutes illness? What is the difference between treatment and healing? How can a personalised service be delivered to patients in a de-personalised and industrialised healthcare system? He looked at the ‘psycho-ecology’ of healing, the meanings we attribute to healing and illness, and the culture of the ailing NHS. Dr Zigmond has an old-school commitment to personal continuity of care and advocacy for his patients. His talk brought an exciting, intriguing, deeply compassionate and humane exploration of the opportunities and challenges facing a GP committed to holistic and personal care.
Dr John Ford : The 20 year Global Burden of Disease Study: a profile for England
Dr Ford presented the results of a research study into the global burden of disease, with particular emphasis on the findings in England. The study ranks countries in terms of several health outcomes referring to different countries’ published health statistics. The data covers the proportion of people who die early or live with a disability, induced by selected diseases such as cardiovascular illness, cancer, stroke and respiratory infections. The study shows a significant decline in health outcomes in England since 2008. In 1990 England ranked 10th best in the world on the measure of early loss of life, or years living with disability, due to the selected diseases. At the end of the study the UK ranked 12th best in the world. Life expectancy for people with those diseases in the UK was increasing during the years leading up to 2009. However from 2009, life expectancy suddenly reduced, and illness induced disability suddenly increased in the UK. This change was more dramatic in the UK than in any of the other developed countries covered in the study.
Professor Paul Whiting : We need to talk about Alzheimer’s
In his talk Professor Whiting outlined his innovative research into the causes, risk factors and treatment of Alzheimer’s. His research is University based and independent of any drug companies. Research into Alzheimer’s has been limited because the drug companies (who fund much of current medical research) consider it not cost effective. Moreover, all recent drug trials have failed. The last drug discovery was in 1992. Paul’s research fills the gap left by by big ‘pharma’. Chemistry, neural science, biology, pharmacology are working together with therapists on the causes of Alzheimer’s and its treatment. The innovative research is achieving some break throughs. However it takes 15 years to get a drug from the initial research, to GP prescription. So any new treatments will be well into the future.