BioScience Today 12

SCIENCETODAY

BIO

MARCHAPRIL2018

- still work to be done

UK AND world News • polio • big interview • salmonella • what is life?

cover story:

The battle against polio

Drug Delivery Devices Innovative developments Customized solutions GMP contract manufacturing

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Welcome

There’s still work to be done but we’re heading in the right direction Ellen Rossiter Editor in chief

Editor Ellen Rossiter ellen.rossiter@distinctivepublishing.co.uk

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Distinctive Publishing or BioScience Today cannot be held responsible for any inaccuracies that may occur, individual products or services advertised or late entries. No part of this publication may be reproduced or scanned without prior written permission of the publishers and BioScience Today.

Welcome to the latest edition of Bioscience Today, turn the pages to find out more about stories that have made a splash in the world of life science over the last few weeks, including some unforgettable Adélie Penguins.

Leaf through this issue and you’ll find a number of stories relating to the workings of the brain.

We welcome the announcement of funding for two key projects: firstly, the new Children’s Brain Tumour Centre of Excellence to be based at the University of Cambridge and The Institute of Cancer Research, London, announced by Cancer Research UK. Secondly, we hear about the £40million awarded to the UK Dementia Research Institute.

In this issue, we also salute the winners of the 2018 Brain Prize, Professors John Hardy, Bart De Strooper, Christian Haass and Michel Goedert – recognising their outstanding and innovative contribution to neuroscience.

In addition, we highlight the upcoming and first truly international research conference to be held on two devastating neurodegenerative diseases, Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), taking place at the Royal College of Physicians in October. Book a place and you’ll have the opportunity to hear one of those Brain Prize award winners. Around 20 speakers from Europe and North America, all leaders in tauopathy research, will share the latest developments in their fields, including neuropathology, biomarkers & imaging, genetics and clinical studies.

We also shine a light on the work of the PSP Association and look at the challenges faced daily by a charity working to support those with conditions that few have heard of and for which there is no funding from central government.

Read more about their remarkable work in this issue, learn why 2017 was an important year for the charity and their hopes for 2018.

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Who can forget the haunting footage of wards filled with children using iron lungs at the height of the Polio outbreak in the midtwentieth Century? In this issue we look back at the battle against Polio; thanks to the successes of the robust immunisation programmes an estimated 1.5 million childhood deaths have been prevented and 16 million people are able to walk today who would otherwise have been paralysed. Yet with the disease still in existence in a few countries, we look at the threat that remains and the work that still needs to be done.

Think that old age and ill health go hand in hand? Well, think again. Researchers at the University of Birmingham and King’s College London are debunking the myths of old age.

After studying a group of cyclists who exercised regularly and a group of adults who did not, researchers found that some of the problems we associate with old age are in fact down to inactivity. In an increasingly sedentary society, the message is clear – whatever exercise you take, take more of it, old age and ill health need not be normal bedfellows – exercise really is the best medicine.

When it comes to the marine world, stickleback fish, cuttlefish and a whale that can mimic human speech all feature in this edition of Bioscience Today. As for seabirds, shortly before we go to press we hear about the discovery of a thriving colony of penguins on the Danger Islands in the Weddell Sea in the East Antarctica Peninsula. Penguinologists have found a large number of Adélie Penguins in the area - a species in decline in other locations – which suggests that penguins flourish where sea ice persists, and in places where climate change and human activity are yet to make an impact.

Researchers are calling for the Weddell Sea Marine Protected Area to be expanded to include the Danger Islands. Turn the page to find out more…

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Unlocking the secrets of a killer

Features

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Ancient genome study identifies traces of indigenous “Taíno” in present-day Caribbean populations

The battle against polio - still work to be done

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Contents 38

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Introduction/Foreword

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Contents

6-23 News Novel Microfluidic platform for Cancer Research

24-25

Polio

The battle against polio - still work to be done

27-31 News

Government nutritional review findings echo dementia

risk messaging

32-35

Big Interview

38-39

Salmonella

42-45

What is life?

Raising awareness of PSP and CBD

Unlocking the secrets of a killer

46 News Killer whale can mimic human speech

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What is life?

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Novel Microfluidic platform for Cancer Research AMSBIO, a transatlantic life sciences company, and the University of Strathclyde (Glasgow, UK) have pioneered a multidisciplinary approach combining expertise in microfluidics and 3D culture to develop a novel microfluidic platform for cancer research.

The new platform combines microfluidic lab-on-a-chip technology with physiologically relevant 3D spheroids to enable formation and long-term culture of 3D multicellular tumors / organoids for drug screening and individualized chemosensitivity testing Extensive testing shows that micro sizing drug-cell interactions reduces cost of experiments significantly as well as increasing productivity as it enables more experiments to be done on the same platform at the same time.

The microfluidic platform delivers precise control over the cellular microenvironment and beneficially through miniaturization, maximizes use of precious limited human cancer samples. Developed using leading-edge microsystem engineering, the platform delivers high-throughput analysis and is fully compatible with automated robotic dispensing systems. To enable customized data analysis of the results from the microfluidic platform, our academic team has also developed a suite of easy-to-use software.

The new microfluidic platform shows great promise to provide a cost-effective approach to applications including high-throughput drug screening and analysis and bioassays to assess spheroid function and morphology. In the area of personalized medicine, it is highly pertinent to not only predict the drug response at early time points during the therapy, but also to be able to identify the optimal drug combination for an individual patient. Within the scope of personalized medicine, this technology presents immense possibilities for testing patient-derived multicellular tumor spheroids/organoids (comprising cancer cells, stromal cells, cancer stem cells and/or immune cells) for disease/ biomarker-oriented drug activity and profiling using singleand pair-wise standard/targeted drug combinations.

For further information on the new microfluidic platform for cancer research please visit www.amsbio-oncoscreen.com or contact AMSBIO on 44-1235-828200/ +1-617-945-5033 / info@amsbio.com.

The microfluidic platform delivers precise control over the cellular microenvironment and beneficially through miniaturization, maximizes use of precious limited human cancer samples.

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THE NEW PLATFORM COMBINES MICROFLUIDIC LAB-ON-A-CHIP TECHNOLOGY WITH PHYSIOLOGICALLY RELEVANT 3D SPHEROIDS

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New Cochrane Review evidence suggests nutritional labelling on menus may reduce our calorie intake New evidence published in the Cochrane Library today shows that adding calorie labels to menus and next to food in restaurants, coffee shops and cafeterias, could reduce the calories that people consume, although the quality of evidence is low.

Eating too many calories contributes to people becoming overweight and increases the risks of heart disease, diabetes and many cancers, which are among the leading causes of poor health and premature death.

Several studies have looked at whether putting nutritional labels on food and non-alcoholic drinks might have an impact on their purchasing or consumption, but their findings have been mixed. Now, a team of Cochrane researchers has brought together the results of studies evaluating the effects of nutritional labels on purchasing and consumption in a systematic review.

The team reviewed the evidence to establish whether and by how much nutritional labels on food or non-alcoholic drinks affect the amount of food or drink people choose, buy, eat or drink. They considered studies in which the labels had to include information on the nutritional or calorie content of the food or drink. They excluded those including only logos (e.g. ticks or stars), or interpretative colours (e.g. ‘traffic light’ labelling) to indicate healthier and unhealthier foods. In total, the researchers included evidence from 28 studies, of which 11 assessed the impact of nutritional labelling on purchasing and 17 assessed the impact of labelling on consumption.

showed that such labels could reduce calories consumed by about 12% per meal. The team noted that there was still some uncertainty around this effect and that further well conducted studies are needed to establish the size of the effect with more precision.

The Review’s lead author, Professor Theresa Marteau, Director of the Behaviour and Health Research Unit at the University of Cambridge, UK, says: “This evidence suggests that using nutritional labelling could help reduce calorie intake and make a useful impact as part of a wider set of measures aimed at tackling obesity,” She added, “There is no ‘magic bullet’ to solve the obesity problem, so while calorie labelling may help, other measures to reduce calorie intake are also needed.”

Author, Professor Susan Jebb from the University of Oxford commented: “Some outlets are already providing calorie information to help customers make informed choices about what to purchase.

This review should provide policymakers with the confidence to introduce measures to encourage or even require calorie labelling on menus and next to food and non-alcoholic drinks in coffee shops, cafeterias and restaurants.”

The team combined results from three studies where calorie labels were added to menus or put next to food in restaurants, coffee shops and cafeterias. For a typical lunch with an intake of 600 calories, such as a slice of pizza and a soft drink, labelling may reduce the energy content of food purchased by about 8% (48 calories). The authors judged the studies to have potential flaws that could have biased the results.

Combining results from eight studies carried out in artificial or laboratory settings could not show with certainty whether adding labels would have an impact on calories consumed. However, when the studies with potential flaws in their methods were removed, the three remaining studies

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The researchers were unable to reach firm conclusions about the effect of labelling on calories purchased from grocery stores or vending machines because of the limited evidence available. They also added that future research would also benefit from a more diverse consideration of the possible wider impacts of nutritional labelling including impacts on those producing and selling food, as well as consumers.

Professor Ian Caterson, President of the World Obesity Federation, commented: “Energy labelling has been shown to be effective: people see it and read it and there is a resulting decrease in calories purchased. This is very useful to know – combined with a suite of other interventions, such changes will help slow and eventually turnaround the continuing rise in body weight.”

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£42m new research institute to boost evidence on improving care in the NHS A new research institute is seeking to create a world-leading asset for the NHS by improving the science behind healthcare organisation and delivery.

The Healthcare Improvement Studies Institute (THIS Institute), led by the University of Cambridge, is made possible by the largest single grant ever made by the Health Foundation, an independent charity. The new institute is founded on the principle that efforts to improve care should always be based on the best quality of evidence. Some of that evidence will be created by NHS patients and staff themselves, using innovative citizen science methods in large-scale research projects.

Director of THIS Institute Professor Mary Dixon-Woods, said: “If you ask people to describe the future of healthcare, they might describe a shiny vision of new treatments and technologies. These kinds of innovations are important.

But how healthcare is organised and delivered, including its basic systems and processes, has perhaps just as much impact, and sometimes more, on patient outcomes and experience.”

Dr Jennifer Dixon, Chief Executive of the Health Foundation, said: “The UK population clearly wants a high quality and sustainable NHS into the future. Understanding what works, in which contexts and why, is crucial, as is

obtaining that evidence fast so it can be acted on. There couldn’t be a more important time to do this, and that is why the Health Foundation has put its money where its mouth is.”

One way the institute will create the evidence-base is through citizen science. Using methods already used in other areas such as biology and astronomy, THIS Institute is building a digital platform to crowdsource research ideas and collect research data from NHS staff and patients, including their opinions on the right indicators of quality of care and their views on equipment design.

Professor Dixon-Woods, Director, THIS Institute, adds: “Tackling healthcare challenges needs to involve a greater variety of people with diverse experience: the institute is looking for expertise in new places. Some of this expertise will come directly from patients – us, you, me – working alongside healthcare staff and other professionals such as engineers and designers.”

The institute will be based at the Cambridge Biomedical Campus, alongside Cambridge University Hospitals NHS Foundation Trust and world-leading research institutes.

It is made possible by a ten-year grant from the Health Foundation, whose mission is to bring about better health and healthcare for people in the UK.

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TACKLING HEALTHCARE CHALLENGES NEEDS TO INVOLVE A GREATER VARIETY OF PEOPLE WITH DIVERSE EXPERIENCE: THE INSTITUTE IS LOOKING FOR EXPERTISE IN NEW PLACES.

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Shoals of sticklebacks differ in their collective personalities

Research from the University of Cambridge has revealed that, among schooling fish, groups can have different collective personalities, with some shoals sticking closer together, being better coordinated, and showing clearer leadership than others.

For centuries, scientists and non-scientists alike have been fascinated by the beautiful and often complex collective behaviour of animal groups, such as the highly synchronised movements of flocks of birds and schools of fish. Often, those spectacular collective patterns emerge from individual group members using simple rules in their interactions, without requiring global knowledge of their group.

In recent years it has also become apparent that, across the animal kingdom, individual animals often differ considerably and consistently in their behaviour, with some individuals being bolder, more active, or more social than others.

New research conducted at the University of Cambridge’s Department of Zoology suggests that observations of different groups of schooling fish could provide important insights into how the make-up of groups can drive collective behaviour and performance.

In the study, published today in the journal Proceedings of the Royal Society B, the researchers created random groups of wild-caught stickleback fish and subjected them repeatedly to a range of environments that included open spaces, plant cover, and patches of food.

Dr Jolle Jolles, lead author of the study, now based at the Max Planck Institute for Ornithology, said: “By filming the schooling fish from above and tracking the groups’ movements in detail, we found that the randomly composed shoals showed profound differences in their collective behaviour that persisted across different ecological contexts. Some groups were consistently faster, better coordinated, more cohesive, and showed clearer leadership structure than others.

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“That such differences existed among the groups is remarkable as individuals were randomly grouped with others that were of similar age and size and with which they had very limited previous social contact.”

This research shows for the first time that, even among animals where group membership changes frequently over time and individuals are not very strongly related to each other, such as schooling fish or flocking birds, stable differences can emerge in the collective performance of animal groups.

Such behavioural variability among groups may directly affect the survival and reproductive success of the individuals within them and influence how they associate with one another. Ultimately these findings may therefore help understand the selective pressures that have shaped social behaviour.

Dr Andrea Manica, co-author of the paper from the University of Cambridge, added: “Our research reveals that the collective performance of groups is strongly driven by their composition, suggesting that consistent behavioural differences among groups could be a widespread phenomenon in animal societies.”

These research findings provide important new insights that may help explain and predict the performance of social groups, which could be beneficial in building human teams or constructing automated robot swarms.

The research was supported by the Biotechnology and Biological Sciences Research Council.

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Study in mice suggests personalised stem cell treatment may offer relief for progressive MS Luca Peruzzotti-Jametti

Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis (MS).

Our mouse study suggests that using a patient’s reprogrammed cells could provide a route to personalised treatment of chronic inflammatory diseases, including progressive forms of MS The study, led by researchers at the University of Cambridge, is a step towards developing personalised treatments based on a patient’s own skin cells for diseases of the central nervous system (CNS).

In MS, the body’s own immune system attacks and damages myelin, the protective sheath around nerve fibres, causing disruption to messages sent around the brain and spinal cord. Symptoms are unpredictable and include problems with mobility and balance, pain, and severe fatigue.

Key immune cells involved in causing this damage are macrophages (literally ‘big eaters’), which ordinarily serve to attack and rid the body of unwanted intruders.

A particular type of macrophage known as microglia are found throughout the brain and spinal cord – in progressive forms of MS, they attack the CNS, causing chronic inflammation and damage to nerve cells.

Recent advances have raised expectations that diseases of the CNS may be improved by the use of stem cell therapies. Stem cells are the body’s ‘master cells’, which can develop into almost any type of cell within the body.

Previous work from the Cambridge team has shown that transplanting neural stem cells (NSCs) – stem cells that are part-way to developing into nerve cells – reduces inflammation and can help the injured CNS heal.

However, even if such a therapy could be developed, it would be hindered by the fact that such NSCs are sourced from embryos and therefore cannot be obtained in large enough quantities. Also, there is a risk that the body will see them as an alien invader, triggering an immune response to destroy them.

A possible solution to this problem would be the use of so-called ‘induced neural stem cells (iNSCs)’ – these cells can be generated by taking an adult’s skin cells and ‘reprogramming’ them back to become neural stem cells.

As these iNSCs would be the patient’s own, they are less likely to trigger an immune response.

Now, in research published in the journal Cell Stem Cell, researchers at the University of Cambridge have shown that iNSCs may be a viable option to repairing some of the damage caused by MS. Using mice that had been manipulated to develop MS, the researchers discovered that chronic MS leads to significantly increased levels of succinate, a small metabolite that sends signals to macrophages and microglia, tricking them into causing inflammation, but only in cerebrospinal fluid, not in the peripheral blood.

Transplanting NSCs and iNSCs directly into the cerebrospinal fluid reduces the amount of succinate, reprogramming the macrophages and microglia – in essence, turning ‘bad’ immune cells ‘good’. This leads to a decrease in inflammation and subsequent secondary damage to the brain and spinal cord.

“Our mouse study suggests that using a patient’s reprogrammed cells could provide a route to personalised treatment of chronic inflammatory diseases, including progressive forms of MS,” says Dr Stefano Pluchino, lead author of the study from the Department of Clinical Neurosciences at the University of Cambridge.

“This is particularly promising as these cells should be more readily obtainable than conventional neural stem cells and would not carry the risk of an adverse immune response.”

Dr Luca Peruzzotti-Jametti, the first author of the study and a Wellcome Trust Research Training Fellow, says: “We made this discovery by bringing together researchers from diverse fields including regenerative medicine, cancer, mitochondrial biology, inflammation and stroke and cellular reprogramming. Without this multidisciplinary collaboration, many of these insights would not have been possible.”

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Study of problems in OCD helps young people unlock their potential at school Barbara Sahakian Adolescents with obsessive-compulsive disorder (OCD) have widespread learning and memory problems, according to research published today. The findings have already been used to assist adolescents with OCD obtain the help they needed at school to realise their potential – including helping one individual go on to university.

I was surprised and concerned to see such broad problems of learning and memory in these young people so early in the course of OCD OCD in children and adolescents is a distressing condition, which is often chronic and persists into adulthood. Almost 90% of these young patients have problems at school, home, or socially; with difficulties doing homework and concentrating at school being the two most common problems. Children and adolescents are well set up for learning and, indeed, can quickly pick up new foreign languages, computing skills or motor tasks, such as riding a bike, much quicker than older adults. But if an adolescent is not learning well in school, they are likely to become stressed and anxious.

Researchers at the University of Cambridge have previously shown that there are core problems of cognitive inflexibility in adults with OCD. Since flexibility in problem-solving is an important skill for performance in school, they wanted to study whether adolescents with OCD had difficulty in this area. Cognitive flexibility becomes important when trying to find the correct solutions to a problem, particularly when your first attempt at solving that problem does not work.

To reach the correct solution, you have to switch to a new approach from the one you have previously been using.

WHILE MANY STUDIES HAVE FOCUSED ON ADULT OCD, WE ACTUALLY KNOW VERY LITTLE ABOUT THE CONDITION IN TEENAGERS.

In healthy individuals, there is a balance between goaldirected control and habit control, and this balance is crucial for daily functioning. For example, when learning to drive, we focus on specific goals, such as travelling at the right speed, staying within the traffic lines and following safety rules. We often have strategies to perform these tasks optimally. However, once we are an experienced driver, we frequently find that driving becomes habitual. In new situations, healthy people tend to use goal-directed control; however, under conditions of stress, they frequently select habitual learning.

In a new study published in the journal Psychological Medicine, researchers looked at whether cognitive flexibility for learning tasks and goal-directed control was impaired early in the development of OCD. The study was led by Dr Julia Gottwald and Professor Barbara Sahakian from the Department of Psychiatry.

Thirty-six adolescents with OCD and 36 healthy young people completed learning and memory tasks. These computerised tests included recognition memory (remembering which of two objects they had seen before) and episodic memory (where in space they remember seeing an object). A subset of 30 participants in each group

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also carried out a task designed to assess the balance of goal-directed and habitual behavioural control.

The researchers found that adolescent patients with OCD had impairments in all learning and memory tasks. The study also demonstrated for the first time impaired goaldirected control and lack of cognitive plasticity early in the development of OCD. Dr Julia Gottwald, the study’s first author, comments: “While many studies have focused on adult OCD, we actually know very little about the condition in teenagers. Our study suggests that teens with OCD have problems with memory and the ability to flexibly adjust their actions when the environment changes.”

Professor Barbara Sahakian, senior author, says: “I was surprised and concerned to see such broad problems of learning and memory in these young people so early in the course of OCD. It will be important to follow this study up to examine these cognitive problems further and in particular to determine how they impact on clinical symptoms and school performance.”

Experiencing learning and memory problems at school could affect self-esteem. Furthermore, some symptoms seen in people with OCD, such as compulsive checking, may result from them having reduced confidence in their memory ability. The stress of having difficulty in learning may also start a negative influence and promote inflexible habit learning.

Dr Anna Conway Morris commented: “This study has been very useful in assisting adolescents with OCD with the help they needed at school in terms of structuring the environment to ensure that there was a level playing field.

This allowed them to receive the help they needed to realise their potential.

“One person with OCD was able to obtain good A Levels and to be accepted by a good university where she could get the support that she needed in order to do well in that environment.”

Future studies will examine in more detail the nature of these impairments and how they might affect clinical symptoms and school performance.

The research was funded by the Wellcome Trust and the Medical Research Council.

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Ancient genome study identifies traces of indigenous “Taíno” in present-day Caribbean populations Eske Willerslev

A thousand-year-old tooth has provided genetic evidence that the so-called “Taíno”, the first indigenous Americans to feel the full impact of European colonisation after Columbus arrived in the New World, still have living descendants in the Caribbean today.

It has always been clear that people in the Caribbean have Native American ancestry, but it was difficult to prove whether this was specifically indigenous to the Caribbean, until now.

Comparing the ancient Bahamian genome to those of contemporary Puerto Ricans, the researchers found that they were more closely related to the ancient Taíno than any other indigenous group in the Americas. However, they argue that this characteristic is unlikely to be exclusive to Puerto Ricans alone and are convinced that future studies will reveal similar genetic legacies in other Caribbean communities.

Researchers were able to use the tooth of a woman found in a cave on the island of Eleuthera in the Bahamas to sequence the first complete ancient human genome from the Caribbean. The woman lived at some point between the 8th and 10th centuries, at least 500 years before Columbus made landfall in the Bahamas.

The findings are likely to be especially significant for people in the Caribbean and elsewhere who have long claimed indigenous Taíno heritage, despite some historical narratives that inaccurately brand them “extinct”. Such misrepresentations have been heavily criticised by historians and archaeologists, as well as by descendant communities themselves, but until now they lacked clear genetic evidence to support their case.

The results provide unprecedented insights into the genetic makeup of the Taíno – a label commonly used to describe the indigenous people of that region. This includes the first clear evidence that there has been some degree of continuity between the indigenous peoples of the Caribbean and contemporary communities living in the region today.

The study was carried out by an international team of researchers led by Dr Hannes Schroeder and Professor Eske Willerslev of Cambridge’s Department of Zoology within the framework of the ERC Synergy project NEXUS1492. The findings are published in the journal Proceedings of the National Academy of Sciences (PNAS).

Such a link had previously been suggested by other studies based on modern DNA. None of these, however, was able to draw on an ancient genome. The new research finally provides concrete proof that indigenous ancestry in the region has survived to the present day.

Schroeder, from the University of Copenhagen who carried out the research as part of the NEXUS1492 project, said: “It’s a fascinating finding. Many history books will tell you that the indigenous population

“It has always been clear that people in the Caribbean have Native American ancestry, but because the region has such a complex history of migration, it was difficult to prove whether this was specifically indigenous to the Caribbean, until now.”

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of the Caribbean was all but wiped out, but people who self-identify as Taíno have always argued for continuity. Now we know they were right all along: there has been some form of genetic continuity in the Caribbean.”

Willerslev, who has dual posts at St John’s College, University of Cambridge, and the University of Copenhagen, said: “It has always been clear that people in the Caribbean have Native American ancestry, but because the region has such a complex history of migration, it was difficult to prove whether this was specifically indigenous to the Caribbean, until now.”

The researchers were also able to trace the genetic origins of the indigenous Caribbean islanders, showing that they were most closely related to Arawakan-speaking groups who live in parts of northern South America today. This suggests that the origins of at least some the people who migrated to the Caribbean can be traced back to the Amazon and Orinoco Basins, where the Arawakan languages developed.

The Caribbean was one of the last parts of the Americas to be populated by humans starting around 8,000 years ago. By the time of European colonization, the islands were a complex patchwork of different societies and cultures. The “Taíno” culture was dominant in the Greater, and parts of the Lesser Antilles, as well as the Bahamas, where the people were known as Lucayans.

To trace the genetic origins of the Lucayans the researchers compared the ancient Bahamian genome with previously published genome-wide datasets for over 40 present-day indigenous groups from the Americas. In addition, they looked

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for traces of indigenous Caribbean ancestry in presentday populations by comparing the ancient genome with those of 104 contemporary Puerto Ricans included in the 1000 Genomes Project. The 10-15% of Native American ancestry in this group was shown to be closely related to the ancient Bahamian genome.

Jorge Estevez, a Taíno descendant who works at the National Museum of the American Indian in New York and assisted the project team, said that as a boy growing up in the United States, he was told stories about his Taíno ancestors at home, but at school was taught that the same ancestors had died out. “I wish my grandmother were alive today so that I could confirm to her what she already knew,” he added. “It shows that the true story is one of assimilation, certainly, but not total extinction. I am genuinely grateful to the researchers. Although this may have been a matter of scientific inquiry for them, to us, the descendants, it is truly liberating and uplifting.”

Although indigenous Caribbean communities were island-based, the researchers found very little genomic evidence of isolation or inbreeding in the ancient genome.

This reinforces earlier genetic research led by Willerslev, which suggests that early human communities developed surprisingly extensive social networks, long before the term had digital connotations. It also echoes ongoing work by researchers at the Faculty of Archaeology in Leiden and others indicating the connectedness of indigenous Caribbean communities.

Professor Corinne Hofman from Leiden University and PI of the NEXUS1492 project, said: “Archaeological evidence has always suggested that large numbers of people who settled the Caribbean originated in South America, and that they maintained social networks that extended far beyond the local scale. Historically, it has been difficult to back this up with ancient DNA because of poor preservation, but this study demonstrates that it is possible to obtain ancient genomes from the Caribbean and that opens up fascinating new possibilities for research.”

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Cambridge University and Institute of Cancer Research launch Children’s Brain Tumour Centre of Excellence Richard Gilbertson

Cancer Research UK (CRUK) has announced funding for a new Children’s Brain Tumour Centre of Excellence, based at the University of Cambridge and The Institute of Cancer Research, London.

The announcement comes as the Health and Social Care Secretary Jeremy Hunt committed an estimated £20 million in funding to tackle brain tumours and deliver a “step change” in survival rates. The funding will be invested through the National Institute for Health Research over the next five years – with the aim of doubling this once new high-quality research proposals become available.

By creating a hub of expertise for childhood brain tumour research in the UK, we aim to make real inroads to tackling these diseases

Each year around 11,400 people in the UK are diagnosed with a brain tumour and just 14% of people survive their disease for 10 or more years.

The announcement comes as CRUK announces an investment of an extra £25 million over the next five years into brain tumour research. This is in addition to the £13 million spent each year on research and development of new treatments for the disease.

Jeremy Hunt MP said: “While survival rates for most cancers are at record levels, the prognosis for people with brain tumours has scarcely improved in over a generation.

Cancer Research UK’s funding will support two new specialised centres. The first of these, the Children’s Brain Tumour Centre of Excellence, brings together world-leading experts to discover and develop new treatments to tackle brain tumours in children. A second centre focusing on adult brain tumours will open later in the year.

The Centre will be led by childhood brain tumour expert Professor Richard Gilbertson, Director of the Cancer Research UK Cambridge Centre.

“By creating a hub of expertise for childhood brain tumour research in the UK, we aim to make real inroads to tackling these diseases,” said Professor Gilbertson. “Gathering this expertise together means we can shine a light on the numerous challenges and difficulties that brain tumours pose and discover new treatments to ensure that more children survive their disease.”

“Our ambition is to deliver a big uplift in the funding of brain cancer research, while galvanising the clinical and scientific communities to explore new avenues for diagnosis and treatment in the future – it is a chance to create a genuine, step change in survival rates for one of the deadliest forms of cancer.”

Sir Harpal Kumar, Cancer Research UK’s chief executive, added: “Brain tumours remain a huge challenge, with survival barely improving over the last 30 years. Since we laid out our plans to tackle this challenge in 2014, Cancer Research UK has already substantially increased its funding into brain tumours and attracted some of the world’s leading experts to the UK. “This new funding will mean that we can accelerate these efforts further, by developing a critical mass of expertise in key areas and supporting work along the entire research pipeline to improve survival for children and adults with brain tumours.”

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Scientists discover the secrets behind the cuttlefish’s 3D ‘invisibility cloak’ Trevor Wardill An international team of scientists has identified the neural circuits that enable cuttlefish to change their appearance in just the blink to eye – and discovered that this is similar to the neural circuit that controls iridescence in squids.

The sea is full of strange and wondrous creatures, but there are few as bizarre and intelligent as octopuses and cuttlefish. We’ve seen dozens of examples of these animals suddenly appearing from nowhere, as if they have thrown off an invisibility cloak Cuttlefish and octopuses are remarkable creatures. They have the ability to change their appearance in a matter of seconds, camouflaging themselves from predators and enabling them to surprise their prey. However, unlike a number of reptiles and amphibians which merely change colour to blend into their surroundings, these cephalopods are also able to change the physical texture of their skin to match the coarseness of surrounding rocks, coral or seaweed.

“The sea is full of strange and wondrous creatures, but there are few as bizarre and intelligent as octopuses and cuttlefish,” says Dr Trevor Wardill from the Department of Physiology, Development and Neuroscience at the University of Cambridge. “We’ve seen dozens of examples of these animals suddenly appearing from nowhere, as if they have thrown off an invisibility cloak. How they do this has long remained a mystery.”

The skin of these animals is covered in tiny muscular organs known as ‘chromatophores’ that change colour in response to a signal from the brain. It also has a second set of muscular organs that can be activated to create bumps known as ‘papillae’. When stimulated, each papilla can change the texture of the skin from flat to three dimensional. The papillae can serve several functions, including disguise.

“WE’VE SEEN DOZENS OF EXAMPLES OF THESE ANIMALS SUDDENLY APPEARING FROM NOWHERE, AS IF THEY HAVE THROWN OFF AN INVISIBILITY CLOAK. HOW THEY DO THIS HAS LONG REMAINED A MYSTERY.”

Understanding the nervous system of these creatures and how they manipulate their skin has proved challenging, but now a team of scientists from the Marine Biological Laboratory and University of Cambridge has begun to understand how this happens. Their results are published today in the journal iScience.

The researchers found that the instruction signal from the cuttlefish’s brain is routed through the stellate ganglion, a peripheral nerve centre. The stellate ganglion houses the giant axon system, so called because it is large enough to see with the naked eye. It also houses particular motor neurons that control the papillae on the mantle (the cuttlefish’s outer surface). This nerve circuitry is similar to that by which squids control skin iridescence.

The giant axon system, due to its large size of up to 1mm, helped Nobel prize-winning Cambridge scientists Alan Hodgkin and Andrew Huxley, along with Australian scientist John Eccles, figure out how nerve impulses (action potentials) work.

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European cuttlefish (Sepia officinalis). Credit: Roger Hanlon Dr Paloma Gonzalez-Bellido, also from the University of Cambridge, adds: “This discovery is really interesting from an evolutionary point of view. It opens up the question of which came first: was the common ancestor to cuttlefish and squid able to camouflage themselves using papillae or express iridescence, or possibly both?”

The researcher team – including Lexi Scaros of Dalhousie University and Roger Hanlon of the Marine Biological Laboratory – also looked in greater detail at the papillae to find out how they manage to hold their shape over a long period of time without a signal. They found that the papillae use a mechanism which they describe as being ‘catch-like’.

It resembles the ‘catch’ mechanism found in bivalves, such as oysters, mussels, and scallops, which enables the bivalve shell to remain closed without expending much energy.

“There is still a big mystery, however, which is how these animals interpret the world around them and translate this into signals that change their appearance,” says Dr Wardill.

The researchers say that understanding how cephalopods’ skin changes from a smooth, flat surface to a textured, 3D structure could help in the design of biologically-inspired materials that can themselves be assembled from flat materials.

“This research on neural control of flexible skin, combined with anatomical studies of the novel muscle groups that enable such shape-shifting skin, has applications for the development of new classes of soft materials that can be engineered for a wide array of uses in industry, society, and medicine,” adds Professor Roger Hanlon of the Marine Biological Laboratory.

The research was largely funded by the US Air Force Office of Scientific Research and the UK Biotechnology and Biological Sciences Research Council.

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| BIOSCIENCE TODAY SPRING 2018 |

AI ‘scientist’ finds that toothpaste ingredient may help fight malaria An ingredient commonly found in toothpaste could be employed as an anti-malarial drug against strains of malaria parasite that have grown resistant to one of the currently-used drugs. This discovery, led by researchers at the University of Cambridge, was aided by Eve, an artificially-intelligent ‘robot scientist’.

Drug-resistant malaria is becoming an increasingly significant threat in Africa and south-east Asia, and our medicine chest of effective treatments is slowly depleting When a mosquito infected with malaria parasites bites someone, it transfers the parasites into their bloodstream via its saliva. These parasites work their way into the liver, where they mature and reproduce. After a few days, the parasites leave the liver and hijack red blood cells, where they continue to multiply, spreading around the body and causing symptoms, including potentially life-threatening complications.

Malaria kills over half a million people each year, predominantly in Africa and south-east Asia. While a number of medicines are used to treat the disease, malaria parasites are growing increasingly resistant to these drugs, raising the spectre of untreatable malaria in the future.

Now, in a study published today in the journal Scientific Reports, a team of researchers employed the Robot Scientist ‘Eve’ in a high-throughput screen and discovered that triclosan, an ingredient found in many toothpastes, may help the fight against drug-resistance.

When used in toothpaste, triclosan prevents the build-up of plaque bacteria by inhibiting the action of an enzyme known as enoyl reductase (ENR), which is involved in the production of fatty acids.

Scientists have known for some time that triclosan also inhibits the growth in culture of the malaria parasite Plasmodium during the blood-stage, and assumed that this was because it was targeting ENR, which is found in the liver. However, subsequent work showed that improving triclosan’s ability to target ENR had no effect on parasite growth in the blood.

says Professor Steve Oliver from the Cambridge Systems Biology Centre and the Department of Biochemistry at the University of Cambridge. “The search for new medicines is becoming increasingly urgent.”

Because triclosan inhibits both ENR and DHFR, the researchers say it may be possible to target the parasite at both the liver stage and the later blood stage.

Lead author Dr Elizabeth Bilsland, now an assistant professor at the University of Campinas, Brazil, adds: “The discovery by our robot ‘colleague’ Eve that triclosan is effective against malaria targets offers hope that we may be able to use it to develop a new drug. We know it is a safe compound, and its ability to target two points in the malaria parasite’s lifecycle means the parasite will find it difficult to evolve resistance.”

Robot scientist Eve was developed by a team of scientists at the Universities of Manchester, Aberystwyth, and Cambridge to automate – and hence speed up – the drug discovery process by automatically developing and testing hypotheses to explain observations, run experiments using laboratory robotics, interpret the results to amend their hypotheses, and then repeat the cycle, automating highthroughput hypothesis-led research.

Professor Ross King from the Manchester Institute of Biotechnology at the University of Manchester, who led the development of Eve, says: “Artificial intelligence and machine learning enables us to create automated scientists that do not just take a ‘brute force’ approach, but rather take an intelligent approach to science. This could greatly speed up the drug discovery progress and potentially reap huge rewards.”

The research was supported by the Biotechnology & Biological Sciences Research Council, the European Commission, the Gates Foundation and FAPESP (São Paulo Research Foundation).

Working with ‘Eve’, the research team discovered that in fact, triclosan affects parasite growth by specifically inhibiting an entirely different enzyme of the malaria parasite, called DHFR. DHFR is the target of a well-established antimalarial drug, pyrimethamine; however, resistance to the drug among malaria parasites is common, particularly in Africa. The Cambridge team showed that triclosan was able to target and act on this enzyme even in pyrimethamineresistant parasites.

“Drug-resistant malaria is becoming an increasingly significant threat in Africa and south-east Asia, and our medicine chest of effective treatments is slowly depleting,”

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“DRUG-RESISTANT MALARIA IS BECOMING AN INCREASINGLY SIGNIFICANT THREAT IN AFRICA AND SOUTH-EAST ASIA, AND OUR MEDICINE CHEST OF EFFECTIVE TREATMENTS IS SLOWLY DEPLETING.”

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Calcium may play a role in the development of Parkinson’s disease Researchers have found that excess levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson’s disease.

This is the first time we’ve seen that calcium influences the way alpha-synuclein behaves.

The international team, led by the University of Cambridge, found that calcium can mediate the interaction between small membranous structures inside nerve endings, which are important for neuronal signalling in the brain, and alpha-synuclein, the protein associated with Parkinson’s disease. Excess levels of either calcium or alpha-synuclein may be what starts the chain reaction that leads to the death of brain cells.

The findings, reported in the journal Nature Communications, represent another step towards understanding how and why people develop Parkinson’s.

According to the charity Parkinson’s UK, one in every 350 adults in the UK – an estimated 145,000 in all – currently has the condition, but as yet it remains incurable.

Parkinson’s disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the sign of Parkinson’s disease.

Curiously, it hasn’t been clear until now what alphasynuclein actually does in the cell: why it’s there and what it’s meant to do. It is implicated in various processes, such as the smooth flow of chemical signals in the brain and the movement of molecules in and out of nerve endings, but exactly how it behaves is unclear.

“Alpha-synuclein is a very small protein with very little structure, and it needs to interact with other proteins or structures in order to become functional, which has made it difficult to study,” said senior author Dr Gabriele Kaminski Schierle from Cambridge’s Department of Chemical Engineering and Biotechnology.

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Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behaviour of alpha-synuclein. To do so, Kaminski Schierle and her colleagues isolated synaptic vesicles, part of the nerve cells that store the neurotransmitters which send signals from one nerve cell to another.

In neurons, calcium plays a role in the release of neurotransmitters. The researchers observed that when calcium levels in the nerve cell increase, such as upon neuronal signalling, the alpha-synuclein binds to synaptic vesicles at multiple points causing the vesicles to come together. This may indicate that the normal role of alpha-synuclein is to help the chemical transmission of information across nerve cells.

“This is the first time we’ve seen that calcium influences the way alpha-synuclein interacts with synaptic vesicles,” said Dr Janin Lautenschlӓger, the paper’s first author. “We think that alpha-synuclein is almost like a calcium sensor.

In the presence of calcium, it changes its structure and how it interacts with its environment, which is likely very important for its normal function.”

“There is a fine balance of calcium and alpha-synuclein in the cell, and when there is too much of one or the other, the balance is tipped and aggregation begins, leading to Parkinson’s disease,” said co-first author Dr Amberley Stephens.

The imbalance can be caused by a genetic doubling of the amount of alpha-synuclein (gene duplication), by an age-related slowing of the breakdown of excess protein, by an increased level of calcium in neurons that are sensitive to Parkinson’s, or an associated lack of calcium buffering capacity in these neurons.

Understanding the role of alpha-synuclein in physiological or pathological processes may aid in the development of new treatments for Parkinson’s disease. One possibility is that drug candidates developed to block calcium, for use in heart disease for instance, might also have potential against Parkinson’s disease.

The research was funded in part by the Wellcome Trust, the Medical Research Council, Alzheimer’s Research UK, and the Engineering and Physical Sciences Research Council.

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| BIOSCIENCE TODAY SPRING 2018 |

The Great British

Biosimilar Journey

Attitudes towards biosimilar drugs have rapidly changed in the last 24 months, but there is still work to do. Divya Chadha Manek from the National Institute for Health Research (NIHR) – the research arm of the UK’s National Health Service - takes stock of the British biosimilar journey so far and hints at where we might be heading next.

Uptake and access to biosimilars in the UK’s National Health Service (NHS) has improved considerably over the last two years. There has been a shift in attitude towards the rituximab biosimilars, compared to the struggles that etanercept and infliximab biosimilars have endured in terms of winning over clinical confidence.

So does the future look bright for upcoming biosimilar medicines that have the NHS in their sights? Without a doubt, there is many a keen eye on the development of biosimilar versions of the blockbuster biologic drug adalimumab, which expects to hit NHS shelves in 2019.

The competition will be lively as there are reported to be between 15 to 20 companies poised to enter the market with an adalimumab biosimilar when the patent expires in October 2018.

NHS England continues to do an excellent job of championing the cause by bringing together key players in the biosimilar field: life sciences industry, patient groups, health professionals and NICE. And their efforts seem to be paying off. A significant step-change came with the launch of NHS England’s Commissioning Framework for Biological Medicines (Including Biosimilar Medicines) in Autumn 2017. The NHS now has an ambitious target of at least 90% of new patients being prescribed the best value biological medicine within 3 months of launch of a biosimilar medicine, and at least 80% of existing patients being switched within 12 months, or sooner if possible.

Yet despite all this work, uptake of biosimilar medicines across the country continues to be varied. In October 2017 the NIHR brought together stakeholders working within the biosimilars arena. Angela McFarlane, Market Development Director for IQVIA, presented data which showed regional variation in NHS trust conversion to biosimilar versions of infliximab, rituximab and etanercept. Angela commented: “There is a lot of work to be done in terms of ironing out variation across England and the NHS England Biologicals Framework will be a key platform for this to happen.”

Indeed, there is still much to do to realise the full cost saving benefits of biosimilar medicines throughout the NHS. And much of it boils down to clinical confidence. Patients and clinicians alike need to feel confident that they will experience the same benefit from a biosimilar medication as from an original biologic drug.

One way to develop and build that confidence is by conducting clinical studies - including real-world evidence studies - here in the UK. Clinical studies will provide both clinicians and patients with the opportunity to utilise new biosimilar medicines in highly controlled context and to generate reliable clinical evidence.

However, in 2016 it came to light that some global life science companies were overlooking the UK as a destination for biosimilar trials. Conversations revealed that some companies were struggling to generate enough interest from clinicians in the UK - citing that clinicians preferred to work with novel drugs. Further investigations revealed that, in many cases, these companies had been targeting key opinion leaders in larger academic institutions. One global CRO told us:

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“We often find that when a sponsor asks us to run a study in the UK they provide us with a list of sites and investigator contacts. But in some cases those contacts may not prove to be the most fruitful; people may have moved jobs, or it may just be that those investigators are based in big research institutions where there is already a lot of similar research taking place and large demands on some patient populations.”

As a result, key opinion leading clinicians decline to participate in the study which could be misinterpreted as apathy for biosimilar medicine trials. However the reality is that the larger NHS/academic institutions, where key opinion leaders tend to be based, make up a fraction of our NHS. The larger portion, made up of multiple types of NHS organisations and NHS service providers, holds enormous potential for biosimilar medicine trials which to date has been largely untapped.

To illuminate that potential, in 2016 the NIHR commenced a scoping exercise of clinical interest within indications that are relevant to biosimilar medicines (cancer, gastroenterology, diabetes, dermatology, rheumatology and ophthalmology). We asked all research-active clinicians across the entire NHS in England for a show of hands if they were interested in delivering trials of biosimilar drugs. The list currently runs at over 800 clinicians and continues to grow.

This resource has become a useful tool for companies wishing to cast their clinical investigator net beyond their usual little black book of contacts.

Armed with this knowledge, the NIHR has begun to actively promoting the UK’s research capacity and capabilities to deliver biosimilar medicine trials to overseas life science companies through its “Focus on Biosimilars campaign” (www.nihr.ac.uk/biosimilars). But this cleverly designed campaign isn’t just aimed at the life sciences industry. It’s also a treasure trove of NHS views and opinions on the benefits of bringing biosimilar medicines into the NHS and is therefore a valuable resource for bolstering clinical confidence. Perhaps hearing it from the horse’s mouth will go some way to easing the concerns of those clinicians who are sitting on the fence.

Meanwhile the education efforts continue. The NIHR is planning to introduce a new online training course to raise awareness of biosimilar medicines and their potential benefits to the NHS. Although it will initially be aimed at NIHR staff, this resource is expected to cascade through to research-active NHS professionals who want to know more about biosimilar medicines. This new resource is currently in development and is expected to be launched in summer 2018.

Nonetheless, the reality is that biosimilars are the new kids on the block. Clinical confidence will grow with time and experience. Bringing more biosimilar medicine clinical trials to the UK will certainly contribute towards improving clinical confidence where efficacy and similarity are concerned. However, some key opinion leaders feel that the longitudinal piece of the biosimilar jigsaw is still missing.

They call for more long-term pharmacovigilance studies of biosimilar medicines similar to BADBIR (British Association of Dermatologist Biologic Interventions Register). BADBIR, led from Manchester, is a UK and Eire observational study seeking to assess the long-term safety of biologic treatments for psoriasis. NICE has recommended that all patients in the UK receiving these new therapies for psoriasis should be registered with BADBIR. Professor Chris Griffiths, Foundation Professor of Dermatology at the University of Manchester and Consultant Dermatologist at Salford Royal NHS Foundation Trust, explains why registries are important: “I’m a practising dermatologist and, for example, we

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know that about 30 per cent of the psoriasis patients in my clinic would not be eligible for clinical trials. This might be because they are either too old, have multiple co-morbidities, or on other drugs which would exclude them from taking part in a trial. Yet these are the patients that we are seeing in the real world when we are using biologic and biosimilar drugs to manage psoriasis. It is this group that probably have the highest risk of adverse events. Thus, real world pharmacovigilance registries, such as the BADBIR study allow us to monitor the longterm safety of these life changing medications.

“This kind of monitoring, and the data it creates, gives both patients and clinicians the added assurance that these drugs are going to perform as well in the real world - as safely and as effectively - as we see in the clinical trials. The BADBIR study has been running for 10 years, and now includes three biosimilar drugs alongside originator drugs. We believe very strongly that the biosimilar drugs should be under the same surveillance as the originator molecules.”

The good news is that the UK is a world leader when it comes to real world research. Professor Martin Gibson, Director of the Greater Manchester branch of the NIHR Clinical Research Network, encapsulates the UK’s real world research strengths: “It’s important to define what we mean by real world research. Real world data is routinely collected clinical information. Real world evidence is distilled from analysing the real world data for example in longitudinal observational studies. In the UK we have invented a third category: real world clinical trials. This is where we run an entire trial using routinely collected clinical data, like we did with the Salford Lung Study.

“The NHS can do all of the above because we have excellent clinical data systems that are becoming more and more linked through the advent of electronic health records and through organisations such as NHS digital. We can also now explore how user-generated information is collected and added to healthcare data to provide even richer longitudinal outcomes that everyone is interested in.

“The NHS is unique because everybody is in it. This means that results we get are generalisable compared to some other healthcare systems where not everybody has the same equality of access to healthcare that we are fortunate to enjoy. This gives us a significant advantage over many other parts of the world.”

Angela McFarlane, IQVIA, agrees: “The UK is the leading real world evidence country in the world. The reason for that is because we have the richest de-identified patient level data set in the world, and of course it’s all in one health system, where every citizen owns a unique NHS number. This is a unique feature which differentiates the UK from the rest of the world in its attractiveness for research and it needs to be capitalised on. Working with the NIHR we hope to bring about a landmark real world evidence study called NHS BioValue which will demonstrate the value of biologics, including biosimilars, in all therapy areas from a patient experience and service impact perspective.”

So what does all this mean for biosimilar medicines uptake in the UK? The hope is that clinical confidence will continue to gather momentum as new biosimilar medicines come to the fore. Clinical research has a key role to play. Whether that is using the NHS as a testbed for new biosimilar medicines, or making the most of the NHS capabilities for long-term post-marketing pharmacovigilance surveillance studies of existing biosimilar drugs. The UK is currently leading Europe in uptake of biosimilar medicines and we have even more to offer.

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| BIOSCIENCE TODAY SPRING 2018 |

Earth holds the key to detecting life beyond our solar system

New research in to how Earth’s atmosphere evolved over time could hold the key to detecting life on exoplanets, according to scientists from the University of St Andrews and Cornell University.

The new study, published in The Astrophysical Journal, details how Earth’s atmosphere evolved over time and how this corresponds to the appearance of different forms of life.

The team, led by Dr Sarah Rugheimer, astronomer and astrobiologist from the School of Earth and Environmental Sciences at the University, studied different geological epochs from Earth’s history, modelling the atmospheres around different stars, bigger and smaller than our Sun. The researchers found that a planet’s star type is an important factor in how an exoplanet’s atmosphere develops and in how detectable signs of life, aka biosignatures, will be.

The study focussed on Earth’s atmosphere at four distinct points in history: before microbes (3.9 billion years ago), after microbes and the first rise of oxygen (2 billion years ago), during the second rise of oxygen (800 million years ago), and Earth as it is today. At each of these points, oxygen, methane and carbon dioxide were in drastically different abundances.

The new findings in to how life evolves in different atmospheres could lay the foundation for scientists to interpret early biosignatures and signs of life on Earth-size exoplanets.

Lead researcher Dr Rugheimer said: “We expect to find a myriad of exoplanets beyond even our wildest imagination.

Even looking back at our own planet, the atmosphere has changed dramatically many times. By looking at the history of Earth and how different host star light would interact with a planet’s atmosphere, we can start to create a grid of models to help us understand future observations.

In particular, in this paper we wanted to find out how detectable biosignature gases have been both in Earth’s history and if these planets were orbiting a different star.”

Varied cloud cover and surface features such as oceans and continents were also factored in during the study to see how these affected the models, however in order to accurately reflect the findings on distant exoplanets larger telescopes are required.

Dr Rugheimer notes: “The 2019 launch of the James Webb Space Telescope should allow us to study a handful of habitable, Earth-size exoplanets transiting red dwarf stars.

The European Extremely Large Telescope, which should be online in the mid-2020s, may also be able to directly image a handful of exoplanets.”

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“WE EXPECT TO FIND A MYRIAD OF EXOPLANETS BEYOND EVEN OUR WILDEST IMAGINATION. EVEN LOOKING BACK AT OUR OWN PLANET, THE ATMOSPHERE HAS CHANGED DRAMATICALLY MANY TIMES.”

| BIOSCIENCE TODAY SPRING 2018 |

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STEM Sussex, helping you engage with the workforce of tomorrow Bronagh Liddicoat Head of STEM Sussex & Engineering UK Employer Support Manager for the South East

At the end of June, almost 10,000 students from across the South East will gather at the South of England Showground for one of the biggest and most important events of the academic year.

Now in its seventh year, the Big Bang Fair South East is one of a series of regional Big Bang Near Me events organised throughout the UK that have given businesses and other employers a unique opportunity to forge links with schools and colleges in their area and to demonstrate the latest innovations in science and technology to potential future workforces.

The Big Bang Fair South East is the culmination of the annual Crawley STEMfest, a two-month-long programme of events in schools and colleges, in STEM Clubs and in the community in general. It is organised by STEM Sussex, the STEM outreach department of the University of Brighton, which works with businesses to inspire young people to pursue further studies, and, hopefully, careers, in science, technology, engineering and maths (STEM).

Crawley STEMfest was launched in 2012, and the first Big Bang Fair South East attracted around 2,000 young people.

This year, for the first time, the event will be held over two days and will be attended by almost 10,000 nine-to-19-yearolds and their teachers, making it an ideal opportunity for employers to reach out to potential future employees.

“The events organised by STEM Sussex help to make students aware of the many training and career opportunities in STEM subjects that are available on their doorstep,” says Bronagh Liddicoat, Engineering UK Employer Support Manager for the South East, who has been involved with Crawley STEMfest since its inception. “They’re exciting and inspiring for both schools and businesses and have had a huge impact on both over the years”.

“At their heart, these events open students’ eyes to careers and futures and highlight the exciting possibilities that exist for young people within STEM. From meeting inspiring

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engineers and scientists from regional employers, and through receiving dedicated careers advice, young people leave an event with a fresh new perspective on where their school subjects can lead them.”

Paula Aldridge, Community Engagement Manager at Gatwick Airport, the Big Bang Fair South East’s headline sponsor, adds: “We’re pleased to be the headline sponsor once again, especially as our sponsorship is enabling the event to take place across two days for the first time”.

“Our objective is to inform young people about the wide range of applications of STEM skills at the airport and to inspire them to choose STEM subjects – helping us to build a pipeline of talent for the future. In return for becoming involved, employers like ourselves are guaranteed to engage with thousands of teachers and students and to have the opportunity to inspire the future workforce and help narrow the local STEM skills gap.”

“Since 2018 is the Year of Engineering, we’re looking forward to celebrating and inspiring a record number of next-generation engineers,” says Estelle Whewell, STEM Sussex Project Manager. “There’s no doubt that for students, educators and employers alike Crawley STEMfest and the Big Bang Fair South East have a long-lasting impact.

“The Big Bang Fair South East is the most exciting and inspiring event in the STEM calendar, and once schools attend, they return year after year. Because of its impact, schools make it an annual date in their academic calendar.

“But the Big Bang Fair South East, the regional STEMfests and the mini-Big Bangs all rely on the continued generosity and support of South East-based employers, scientific, professional and education and outreach organisations, and to reflect the variety of STEM-based career paths, we constantly need to engage with new supporters and funders.”

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| BIOSCIENCE TODAY SPRING 2018 |

Memories can be decoded from brain waves during sleep, say researchers Bursts of brain activity known as sleep spindles can play a vital role in strengthening new memories after learning, researchers have found.

In a study carried out by the Universities of Birmingham and York published in Current Biology, researchers found new insight into the process of memory consolidation during sleep. Their findings could also suggest new ways to help people remember things better, according to the researchers.

Scientists have long known that sleep spindles - sudden bursts of oscillatory brain activity - play an important role in the formation and retention of new memories. Sleep spindles are half-second to two-second bursts of brain activity that occur during deep sleep, and can be visualized and measured on an electroencephalogram (EEG).

Dr Bernhard Staresina, of the University of Birmingham’s School of Psychology, said: “While it has been shown previously that targeted memory reactivation can boost memory consolidation during sleep, we have now showed that sleep spindles might represent the key underlying mechanism.

“Thus, direct induction of sleep spindles - for example, by stimulating the brain with electrodes - perhaps combined with targeted memory reactivation, may enable us to further improve memory performance while we sleep.

“Our data suggest that spindles facilitate processing of relevant memory features during sleep and that this process boosts memory consolidation.”

Dr Scott Cairney, from the University of York’s Department of Psychology, said: “We are quite certain that memories are reactivated in the brain during sleep, but we don’t know the neural processes that underpin this phenomenon.

Earlier studies have shown that the number of spindles that occur during the night could predict a person’s memory the next day. But many questions about the link between sleep spindles and how a person’s recently acquired information is ‘reactivated’ and strengthened during sleep remained.

“Sleep spindles have been linked to the benefits of sleep for memory in previous research, so we wanted to investigate whether these brain waves mediate reactivation. If they support memory reactivation, we further reasoned that it could be possible to decipher memory signals at the time that these spindles took place.

Now the researchers in Birmingham and York have demonstrated that there is a particular pattern of brain activity that supports this reactivation process. This new study has also shown that the content of reactivated memories can be decoded for brain activation patterns at the time that spindles occur.

“We asked participants in our study to learn associations between words and pictures of objects or scenes before a nap. Half of the words were then replayed during the nap to trigger the reactivation of the newly learned picture memories.

The team devised an experiment in which people learned to associate particular words with particular objects and scenes. Some study participants then took a 90-minute nap after their study session, whereas others stayed awake. While people napped, the researchers cued those associative memories and unfamiliar words. The team monitored the participants’ brain activity during sleep using an EEG machine.

“When the participants woke after a good period of sleep, we presented them again with the words and asked them to recall the object and scene pictures. We found that their memory was better for the pictures that were connected to the words that were presented in sleep, compared to those words that weren’t.”

The results showed them that sleep spindles occurred when memories were reactivated by presenting the associated words.

This new understanding of the way the brain normally processes and strengthens memories during sleep may help to explain how that process may go wrong in people with learning difficulties, according to the researchers. It might also lead to the development of effective interventions designed to boost memory for important information.

Importantly, the researchers were able to differentiate the brain signals associated with reactivated objects and scenes.

This demonstrates that spindles produce a specific code for the content of reactivated memories - a process that may underpin our ability to remember more after sleep.

Dr Cairney said: “When you are awake you learn new things, but when you are asleep you refine them, making it easier to retrieve them and apply them correctly when you need them the most. This is important for how we learn but also for how we might help retain healthy brain functions.”

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A lifetime of regular exercise slows down ageing, study finds Researchers at the University of Birmingham and King’s College London have found that staying active keeps the body young and healthy.

The researchers set out to assess the health of older adults who had exercised most of their adult lives to see if this could slow down ageing.

The study recruited 125 amateur cyclists aged 55 to 79, 84 of which were male and 41 were female. The men had to be able to cycle 100 km in under 6.5 hours, while the women had to be able to cycle 60 km in 5.5 hours. Smokers, heavy drinkers and those with high blood pressure or other health conditions were excluded from the study.

The participants underwent a series of tests in the laboratory and were compared to a group of adults who do not partake in regular physical activity. This group consisted of 75 healthy people aged 57 to 80 and 55 healthy young adults aged 20 to 36.

The study showed that loss of muscle mass and strength did not occur in those who exercise regularly. The cyclists also did not increase their body fat or cholesterol levels with age and the men’s testosterone levels also remained high, suggesting that they may have avoided most of the male menopause.

More surprisingly, the study also revealed that the benefits of exercise extend beyond muscle as the cyclists also had an immune system that did not seem to have aged either.

An organ called the thymus, which makes immune cells called T cells, starts to shrink from the age of 20 and makes less T cells. In this study, however, the cyclists’ thymuses were making as many T cells as those of a young person.

The findings come as figures show that less than half of over 65s do enough exercise to stay healthy and more than half of those aged over 65 suffer from at least two diseases.* Professor Janet Lord, Director of the Institute of Inflammation and Ageing at the University of Birmingham, said: “Hippocrates in 400 BC said that exercise is man’s best medicine, but his message has been lost over time and we are an increasingly sedentary society.

“However, importantly, our findings debunk the assumption that ageing automatically makes us more frail.

“Our research means we now have strong evidence that encouraging people to commit to regular exercise throughout their lives is a viable solution to the problem that we are living longer but not healthier.”

Dr Niharika Arora Duggal, also of the University of Birmingham, said: “We hope these findings prevent the danger that, as a society, we accept that old age and disease are normal bedfellows and that the third age of man is something to be endured and not enjoyed.”

Professor Stephen Harridge, Director of the Centre of Human & Aerospace Physiological Sciences at King’s College London, said: “The findings emphasise the fact that the cyclists do not exercise because they are healthy, but that they are healthy because they have been exercising for such a large proportion of their lives.

“Their bodies have been allowed to age optimally, free from the problems usually caused by inactivity. Remove the activity and their health would likely deteriorate.”

Norman Lazarus, Emeritus Professor at King’s College London and also a master cyclist and Dr Ross Pollock, who undertook the muscle study, both agreed that: “Most of us who exercise have nowhere near the physiological capacities of elite athletes.

“We exercise mainly to enjoy ourselves. Nearly everybody can partake in an exercise that is in keeping with their own physiological capabilities.

“Find an exercise that you enjoy in whatever environment that suits you and make a habit of physical activity. You will reap the rewards in later life by enjoying an independent and productive old age.”

The research findings are detailed in two papers published today in Aging Cell and are the result of an ongoing joint study by the two universities, funded by the BUPA foundation.

The researchers hope to continue to assess the cyclists to see if they continue to cycle and stay young.

Professor Janet Lord

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*Kings Fund Report on Multimorbidity 2014 - www.kingsfund.org.uk/projects/ time-think-differently/trends-disease-and-disability-long-term-conditionsmulti-morbidity

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The battle

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against polio - still work to be done

People of a certain age in the Western World will have haunting recollections of a disease that laid waste to vast numbers of young people. A cruel disease that filled sanitoriums with rows of partially—paralysed children. Polio, a name to strike fear into every parent.

Today, it is a different picture with the disease having been eradicated in most countries, all but defeated by scientific advances in vaccines and a rigorous campaign to administer them that, according to the latest statistics, has reduced incidences by a staggering 99.9 per cent.

Time for a celebration? Well, not quite. Bioscientists and health professionals are a cautious bunch and find themselves loathe to talk about diseases being eradicated because they know that the viruses are simply waiting for an opportunity to make a comeback if we let our guard down.

That is why health professionals constantly caution that the battle against polio is not won.

For all this, the picture is a rosy one with only three countries still blighted by the virus, although a number of others are regarded as at risk should health campaigns falter.

Thirty years ago, according to the World Health Organisation (WHO), polio paralysed more than 350,000 children each year in more than 125 countries. The WHO says that since 1988 cases have decreased to just 37 reported cases in 2016.

Of the three strains of wild poliovirus (type 1, type 2, and type 3), wild poliovirus type 2 was eradicated in 1999 and no case of wild poliovirus type 3 has been found since the last reported case in Nigeria in November 2012.

Nevertheless, according to the WHO, serious challenges remain in the final steps to eradicate the virus, largely caused by weak health systems that struggle to vaccinate every child to ensure high enough protection within a community. This becomes a particular concern in areas including remote locations and those hit by conflict.

Leading the efforts to take those final steps to eradication is the Global Polio Eradication Initiative (GPEI), a publicprivate partnership led by national governments with five partners, the World Health Organisation, Rotary International, the US Centers for Disease Control and Prevention, the United Nations Children’s Fund (UNICEF) and the Bill & Melinda Gates Foundation.

It dates back to 1988 and the forty-first World Health Assembly, which adopted a resolution for the worldwide eradication of polio. The decision followed the confirmation that smallpox had been eradicated in 1980, progress during the 1980s towards elimination of the poliovirus in the Americas and Rotary International’s commitment to raise funds to protect children from the disease.

In 1994, the WHO Region of the Americas was certified polio-free, followed by the WHO Western Pacific Region in 2000 and the WHO European Region in June 2002.

Twelve years later, in March 2014, the WHO South-East Asia Region was certified polio-free, meaning that transmission of wild poliovirus had been interrupted in a block of eleven countries stretching from Indonesia to India.

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ACCORDING TO THE LATEST STATISTICS, THE VACCINES HAS REDUCED INCIDENCES BY A STAGGERING 99.9 PER CENT

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The WHO says that the advances mean that 80% of the world’s population now live in certified polio-free regions and that more than 16 million people are able to walk today, who would otherwise have been paralysed. An estimated 1.5 million childhood deaths have also been prevented, through the systematic administration of vitamin A during polio immunisation activities.

The battle may have been won but there is still a war to be waged before those harrowing pictures of paralysed children lining hospital wards are truly designated to history.

However, more needs to be done. For example, contributions and pledges of US$1.2 billion were made at the recent Rotary Convention in Atlanta, USA which was attended by 32, 000 Rotarians from around the world.

Polio factfile

A proportion of the money will help WHO in their work to support countries vaccinate 450 million children per year against polio.

Polio is a highly infectious disease caused by a virus.

It invades the nervous system, and can cause total paralysis in a matter of hours. The virus is transmitted by person-to-person, mainly through the faecal-oral route or, less frequently by contaminated water or food, and multiplies in the intestine. Initial symptoms are fever, fatigue, headache, vomiting, stiffness of the neck and pain in the limbs. 1 in 200 infections leads to irreversible paralysis (usually in the legs). Among those paralysed, 5% to 10% die when their breathing muscles become immobilised.

Dr Tedros Adhanom Ghebreyesus, Director-General of the World Health Organisation, said: “It is humbling to see again the power of this incredible global partnership to generate funding to fight one of the world’s most horrible and debilitating diseases. ”The new pledges show that donors understand the urgent need to support this mission right through to the very end.

We must finish the job properly to ensure that there is no chance of this terrible disease coming back.”

To underline the point, the WHO points to the endemic transmission continuing in Afghanistan, Nigeria and Pakistan.

Failure to stop polio in these last remaining areas puts the world at risk, it argues, and could result within ten years in as many as 200,000 new cases all over the world if left unchecked.

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POLIO AND ITS SYMPTOMS

Polio mainly affects children under five years of age.

There is no cure for polio, it can only be prevented.

Polio vaccine, given multiple times, can protect a child for life.

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| news |

Government nutritional review findings echo dementia risk messaging Alzheimer’s Research UK is backing the findings of a Scientific Advisory Committee on Nutrition (SACN) review on diet and its impact on cognitive impairment and dementia.

The committee has published a report that finds there is no conclusive evidence for nutrients or supplements to be used to prevent the onset of dementia. This is the first time the organisation has reviewed evidence in this area.

Alzheimer’s Research UK, the leading dementia research charity in the UK, supports the findings of the report and is calling for further government support to investigate ways to prevent Alzheimer’s disease and the other diseases that cause dementia.

Dr Matthew Norton, Director of Policy and Impact at Alzheimer’s Research UK, said: “The findings of the Scientific Advisory Committee on Nutrition’s study into diet and dementia echo the weight of evidence available so far in this area. The brain, just like other parts of the body, can be affected by the way we live our lives. While a balanced diet is one way to maintain a healthy brain, the best current evidence suggests supplements or nutrients offer no additional preventative value. Wider evidence points to a number of

other lifestyle factors that can also play a role. Not smoking, staying mentally and physically active, only drinking in moderation and keeping blood pressure and cholesterol in check are all ways to keep the brain healthy into later life.

“The government plays an important role in setting guidelines for healthy living.

From health checks and risk reduction information, to funding more prevention research, Alzheimer’s Research UK believes government plays a key role in dementia prevention.

Last year Alzheimer’s Research UK invested in four new cutting-edge dementia prevention projects including those looking at lifestyle interventions and dietary advice “It is vital the government, alongside academic institutions and charities like Alzheimer’s Research UK, continues to raise awareness of key risk factors of dementia, as well as supporting new research to increase our understanding of the condition.”

Better memory and thinking seen in over 85s despite high cholesterol US scientists have found that high levels of cholesterol in people over the age of 85 is linked with a reduced decline in memory and thinking ability. The findings are published in the scientific journal, Alzheimer’s and Dementia.

Dr David Reynolds, Chief Scientific Officer of Alzheimer’s Research UK, said: “The overwhelming weight of evidence indicates that high cholesterol, especially in midlife, is linked to an increased risk of dementia. It is very difficult to identify a single risk factor for dementia in this selective group of very old people who do not already have the condition. The

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finding that high cholesterol in people over 85 may be linked to better cognitive function, probably reflects the genetic makeup of people who survive to this advanced age rather than the amount of cholesterol in their blood.

“There is no suggestion or evidence from this research that people should increase their cholesterol levels to maintain a healthy brain and we know high cholesterol is a risk factor for many other health conditions. Currently the best evidence to maintain good brain health is to eat a balanced diet, maintain a healthy weight, not smoke, exercise regularly and keep blood pressure and cholesterol in check.

If anyone has concerns about their cholesterol level or any other aspect of their health, they should talk to their doctor.”

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Government announces £300 million for landmark ageing society grand challenge 10 million Brits alive today can expect to reach 100 and funding will ensure the UK leads the world in healthy ageing • The funding will support better diagnosis for UK patients through AI and new tech at new regional centres of excellence • 500,000 Biobank volunteers will see their genome sequenced providing data that will help the UK lead the world in development of tools for early diagnosis and new pioneering therapies • Extra £40 million invested in new hub for UK Dementia Research Institute • New funding will develop new products and services which will help people live in their homes longer, tackle loneliness, and increase independence As part of the government’s plan to build a Britain fit for the future, the Business Secretary Greg Clark has just announced a £300 million competitive fund to develop the innovations and new technologies of tomorrow.

Through the ambitious Industrial Strategy, government is investing over £300 million from its Industrial Strategy Challenge Fund (ISCF) to bring together the UK’s worldclass research expertise with business investment to develop technologies and industries that can help the UK prepare for the challenge of an ageing society.

To ensure taxpayer money is being invested in the right areas, the government set out four Grand Challenges in its Industrial Strategy – priority areas and industries the UK is determined to be at the forefront of in the future where we can lead the global technological revolution, creating more skilled jobs to boost the productivity and earning power of people throughout the UK. Through its Ageing Society Grand Challenge the government has committed to invest in harnessing the power of innovation to help meet the diverse needs of an ageing society.

More than 10 million people in the UK today can expect to see their 100th birthday, compared to the 15,000 centurions today. Ageing populations are a global phenomenon that are creating new demands for technologies, products and services, including new care technologies, different housing models and innovative savings products for retirement.

Welcoming today’s announcement, Business Secretary Greg Clark said: “Through our Industrial Strategy we will not only boost innovation and productivity across the UK, but we will also ensure that this government changes people’s lives for the better.

“We are investing over £300 million into developing the treatments of the future, in new technologies that will revolutionise the way we age and provide everyone with the best possible chance to grow old with dignity in their own home.

“By 2020 we want to be the best country in the world for dementia care and research and today’s announcement of £40 million for the Dementia Research Institute is a vitally important step on that journey.”

Caroline Dinenage, Minister of State for Care said: “As a society we are living longer - a child born today can expect to live to 100 years - but now we must seize the opportunity to improve the quality of lives lived longer. With an increasingly ageing population we must transform the way we think about our work, our housing, our health, our finances and our communities.

“These investments will not only help in our aims to make this the best country in the world to live with dementia but provide a revolutionary vital boost to develop and scale up products and services of the future, ensuring everyone can age well and live more independently throughout their lives.”

HEALTHY AGEING PROGRAMME The £98 million ‘healthy ageing programme’ will drive the development of new products and services which will help people to live in their homes for longer, tackle loneliness, and increase independence and wellbeing.

The new allocation of funding will see the government invest over £300 million to ensure the UK is able to meet these demands, with £98 million for a ‘healthy ageing programme’ and £210 million for a ‘data to early diagnosis and precision medicine programme’ to improve diagnosis of disease and develop new medical treatments and technologies.

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The programme will be investing in tackling some of the toughest medical challenges facing society today.

Separately, with an estimated 850,000 people in the UK living with dementia, the Government has today announced it will be investing an extra £40 million into the UK Dementia Research Institute (UKDRI) to create a new hub in partnership with University College London that will host 350 leading scientists, researching new treatments to improve the lives of millions.

MORE THAN 10 MILLION PEOPLE IN THE UK TODAY CAN EXPECT TO SEE THEIR 100TH BIRTHDAY, COMPARED TO THE 15,000 CENTURIONS TODAY.

Dr Rob Buckle, Chief Science Officer at the Medical Research Council, added “Developing the UK Dementia Research Institute hub in partnership with UCL will bring tremendous benefits for science and for health.

“The new building will provide state-of-the-art facilities for research and the development of new dementia therapies, and will be located alongside neurology clinics and have a dedicated space for engaging dementia patients and their families and carers.”

DATA TO EARLY DIAGNOSIS AND PRECISION MEDICINE PROGRAMME The £210 million investment in the ‘data to early diagnosis and precision medicine’ challenge will see the UK lead the world in the development of innovative new diagnostic tools, medical products and treatments.

As part of the funding announced, the government will be investing in genomics, ensuring the UK continues to lead the world in large scale whole genome sequencing. Genome sequencing can help those with rare diseases receive faster diagnoses and cancer patients gain better access to personalised treatment programmes.

Through the new investment, the UK will sequence the genomes of 500,000 Biobank volunteers. The data from each of these volunteers will provide a rich resource of data that UK researchers will use to build a greater understanding of disease processes and enable the development of tools for early diagnosis and a new wave of therapies.

REGIONAL CENTRES OF EXCELLENCE Over £70 million is going to be invested in creating regional centres across the UK to offer UK patients better diagnosis using new technologies including Artificial Intelligence (AI).

This investment, as well as future funding from industry, in new centres of excellence will support industry collaboration with the NHS to help the UK lead the world in digital pathology and radiology, including using AI to analyse medical images.

Applying AI to medical images has the potential to diagnose disease more accurately and therefore provide more targeted treatment, and increase efficiency in the health system.

Each centre will enable companies, including SMEs, to rapidly develop, test and implement products and systems in partnership with doctors and academics, improving patient care and gaining early evidence of real-world product value.

Investing in these programmes will enable research that could result in globally significant advances in healthcare such as cures for some cancers. The different strands of the ISCF programme will create the data needed to enable research into better diagnosis, treatment and prevention of disease.

The government has also announced the winning bids for the £21m Advanced Therapy Treatment Centres that will be established across the UK by industry, academia and the NHS. Funded by the ISCF Medicines Manufacturing challenge, the centres will be located at Innovate Manchester Advanced Therapy Centre Hub (iMATCH), the Midlands-Wales Advanced Therapy Treatment Centre (MWATTC, comprising Birmingham, Wales and Nottingham) and the Northern Alliance Advanced Therapies Treatment Centre (NAATTC, comprising Scotland, Newcastle and Leeds). The centres will specialise in the delivery of cell and gene therapy products that could treat forms of blindness, cancer, heart failure, liver disease, neurological conditions and rare paediatric diseases and will be coordinated by the Cell and Gene Therapy Catapult. www.gov.uk/government/news/government-announces-300million-for-landmark-ageing-society-grand-challenge

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Professors John Hardy

Christian Haass

Bart De Strooper

Michel Goedert

Top dementia researchers awarded prestigious Brain Prize Pioneering dementia researchers Professors John Hardy, Bart De Strooper, Christian Haass and Michel Goedert have been awarded the prestigious 2018 Brain Prize. The award honours outstanding contribution to neuroscience and recognises their innovative work on the genetic and molecular basis of Alzheimer’s disease.

The four leading researchers will share a collective prize of one million Euros awarded by the Lundbeck Foundation in Denmark. Three of the four recipients, Prof Hardy, Prof De Strooper and Dr Goedert are key players in UK dementia research.

Dr David Reynolds, Chief Scientific Officer at Alzheimer’s Research UK, the UK’s leading dementia research charity, said: “Our congratulations go to all four of these outstanding scientists whose vital contributions have transformed our understanding of the complex causes of Alzheimer’s disease.

The fact that three of these researchers work in the UK reflects the country’s position as a global leader in dementia research and we are proud that Alzheimer’s Research UK

has been able to play a role in supporting their important work.

“Their achievements show how much progress has been made in dementia research in recent decades, and the importance of mechanistic research in shaping the way we study and treat diseases like Alzheimer’s. It is through the dedication and hard work of researchers that we will continue to drive breakthroughs that pave the way for new treatments and provide hope to people with dementia and their families. We look forward to working with these leading scientists in the years to come as they continue to push back the frontiers of our knowledge and take up the biggest challenges in dementia research.”

“Their achievements show how much progress has been made in dementia research in recent decades, and the importance of mechanistic research in shaping the way we study and treat diseases like Alzheimer’s.”

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The First International Research Symposium on PSP & CBD PSPA is delighted to be bringing together the international PSP & CBD research community in 2018.

The first truly international research conference on these two devastating neurodegenerative diseases will take place on 25th and 26th October 2018 at the Royal College of Physicians, London.

Working with colleagues at CurePSP, our USA equivalent, we have put together an exciting programme, with around 20 speakers from Europe and North America.

All leaders in tauopathy research, they will be sharing latest developments from their various fields, including neuropathology, biomarkers & imaging, genetics and clinical studies. We will also be joined by representatives from the pharmaceutical industry, where PSP is now receiving considerable attention as a testbed for tautargeting therapies.

We are pleased that the event is also being supported by the PSP Society of Germany and CBD Solutions from Sweden.

PSPA is keen to facilitate greater collaboration amongst international patient associations in the future.

“Conferences like this provide the perfect environment for establishing new collaborations and generating new directions for studies” says Andrew Symons, PSPA’s Chief Executive. “We are delighted to be working alongside CurePSP to lead the organisation of this event.”

You can view the programme at: www.eventbrite.com/e/ the-first-international-symposium-on-psp-cbdregistration-37916614615?aff=eac2

Prof James Rowe

“Conferences like this provide the perfect environment for establishing new collaborations and generating new directions for studies.”

Changes in the eye connected to a decline in memory Researchers in the US have found that changes in the blood vessels of the eye are associated with a greater decline in people’s memory and language skills over a 20-year period.

Their findings were published in the scientific journal, Neurology.

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, said: “Exploring how our eyes can shed light on changes underway in the brain is an area that is attracting more and more research attention. As the brain is so well protected we can only visualise it indirectly, often through expensive brain scans. The retina offers a potentially valuable window into the brain, and it can be studied with cheaper, noninvasive eye scans.

“While this research highlights a specific change in the retina that may be linked to a decline in memory and thinking skills, it didn’t investigate whether these changes were related to a higher risk of dementia. There is a desperate need for better ways to diagnose the diseases that cause dementia so that people can get access to support, treatments and opportunities to take part in research. Further studies will be needed to evaluate whether techniques like this could one day support doctors making a diagnosis in the clinic and continued investment in research is vital to ensure this progress.”

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Raising awareness of PSP and CBD Ellen Rossiter speaks to Andrew Symons, Chief Executive of PSP Association, about the work of the association and his hopes for the future.

Imagine striving daily to raise awareness of, and to find a cure for, a condition which few have heard of and for which there is no funding from central government. Such is the lot of the dedicated and energetic team at the PSP Association (PSPA).

Andrew Symons

The who? PSPA is the only national charity offering advice, support and information to people living with Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) while supporting research into treatments and ultimately, a cure.

“It’s all about awareness,” comments Andrew Symons, Chief Executive of PSP Association (PSPA), “raising awareness is our biggest challenge.” When explaining where he works, Andrew is often met with consternation and bemusement – so building awareness amongst the general public, medical professionals, and the administrators of medical and related records is a key focus of their work.

PSP and CBD are extremely rare, many medical professionals will go through their entire career without coming across a case, and therein lies their challenge both in raising awareness and in procuring funding. PSP is estimated to affect about six or seven people in every 100,000. Yet understanding and finding a cure for PSP and CBD would not only be a breakthrough for those with these conditions but will deepen our understanding of other related conditions too, including Alzheimer’s and Parkinson’s.

For those not in the know, PSP and CBD are cruel and devastating neurological diseases, caused by the progressive death of nerve cells in the brain, leaving people unable to balance, walk, talk, eat, swallow, drink and see. Typically, people live between five and seven years after the onset of symptoms.

PSP and CBD are associated with an accumulation of a protein called tau in certain parts of the brain; tau is also associated with Alzheimer’s and Parkinson’s. Whilst there are differences between PSP and CBD, many people with CBD do develop features of PSP and vice versa.

An estimated 6,000 people are living with PSP and CBD in the UK, but this number could be more than 10,000 as many are misdiagnosed with other conditions. There is currently no treatment and no cure, but there is hope in the shape of the work undertaken by the PSPA, their supporters and the researchers with whom they work. “Our goal is a world free of PSP and CBD and our three-year strategy is to help people with these conditions lead the best life they can,” continues Andrew.

Andrew came to the role from a commercial background, having worked in change management, corporate services and run his own company too. Having confirmed the sale of his company on a Tuesday, Andrew saw the advert for the Chief Executive’s role on Thursday and duly applied, joining the team in 2017. Andrew had a desire to give something back, but his professional goal also reflected a personal motivation, for Andrew’s father had PSP. PSPA provides information and support for families and helps them access assistance from statutory and other public or voluntary bodies. PSPA is making a difference; greater than 3 in 4 of the users of their frontline services rate them as “very good or excellent”. PSPA is currently supporting 1450 people who have PSP, 289 people with CBD and a further 2,423 people who are supporting someone with these conditions.

Raising awareness amongst health and social care professionals of these devastating diseases, is another of their missions because, with early and accurate diagnosis, people can get the support they need, when they need it. An estimated 40% of people with PSP are misdiagnosed, many Continued on page 34

“Our goal is a world free of PSP and CBD and our three-year strategy is to help people with these conditions lead the best life they can.”

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of whom are initially diagnosed with Parkinson’s. At the moment there are no simple tests or brain scans available to assist with diagnosis – which is why raising awareness amongst the medical professionals and medical students is so important. Conversely, Neurologists who specialise in PSP will recognise someone with PSP almost immediately from their gait.

themselves to run the London Marathon – which is our biggest single fundraising event with many runners raising over £1,000 each, and some, much more. We’ve also been awarded grants from private medical research and other general Trust funds in the UK, and we’ve been the beneficiary of legacies from people who’ve been diagnosed with and subsequently died from PSP or CBD.”

Another of Andrew’s frustrations is the way in which deaths from PSP and CBD are recorded, often giving pneumonia as the cause of death, even though PSP or CBD are at the root. NHS records allow for only one cause of death and all too often PSP and CBD are not mentioned, making gathering accurate statistics even more difficult. So one of the campaigns they are involved in is to raise awareness of these conditions amongst those involved in administering medical records and records of deaths.

The PSP Association was founded by Michael Koe 24 years ago after his wife was diagnosed with the condition, and he found it impossible to find information about the disease. From the start, the work of the association has been visionary. Early steps taken by PSPA included funding the research fellowships of two promising young medics, now those medics are amongst the leading neurologists in the country, based at universities in London and Cambridge; and their research continues.

“We want to modernise the way in which death is recorded,” says Andrew, “we want those involved in administering medical records to provide more accurate records of these diseases, which will help us in building up a more accurate picture of them and help us when it comes to the better allocation of resources.”

“A third of our funding goes into research and a long-term study is underway which will model the progress of the disease. We are desperate to get on with these studies, to find treatments and cures.”

When it comes to funding, “we are financed entirely by voluntary donations,” comments Andrew “and like the majority of UK charities, we receive no funding whatsoever from central government. We depend on donations from our volunteer fundraisers, many of whom go to remarkable lengths to raise funds for us in sponsored events like parachute jumps. As we speak, 72 volunteers are readying

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A landmark for PSPA, has been the creation of the PSP Research Network, co-ordinated from the Institute of Neurology at UCL, headed up by Professor Huw Morris. The Research Network currently incorporates seven primary centres with a strong history of PSP and CBD research and care, plus 15 sub-centres. The network brings together leading experts from many areas of biomedical research, including neuroimaging, clinical analysis, pathology and genetics. It will allow the pooling of patient samples and data and will provide a basis for communication and collaboration through which proposals for further research can be built.

AN ESTIMATED 6,000 PEOPLE ARE LIVING WITH PSP AND CBD IN THE UK, BUT THIS NUMBER COULD BE MORE THAN 10,000 AS MANY ARE MISDIAGNOSED WITH OTHER CONDITIONS.

“A third of our funding goes into research and a long-term study is underway which will model the progress of the disease. We are desperate to get on with these studies, to find treatments and cures,” explains Andrew. The network has embarked on a major study known as PROSPECT. This involves the collection of samples, scanned images and clinical information from a group of patients over several years, enabling researchers to make new discoveries based on the way that PSP changes over time. A separate arm of the study will collect one-off blood samples from patients across the UK, generating a resource for investigating indicators of disease in blood as well as genetic data.

Progress is being made in other areas too, figures from the last financial year show we recruited a record number of local groups in the UK. 2017 has also been an important year for PSPA as they received an historic high in terms of trust fund grants. In the North East, PSPA was awarded £25,000 of funding from the Northumberland Freemasons to raise awareness in the region and to measure the impact of PSPA’s work. PSPA is hoping to use part of the Mason’s funding to appoint an engagement officer in a pilot scheme there to coordinate our fundraising, local group and supporter activity in the region, as well as helping with the education and general of awareness of PSP/CBD amongst health and social care workers. In 2017 PSPA also reached more people than ever before through educational events, and this work continues.

Research has also begun to look at the effectiveness of healthcare delivery in Scotland, tackling one of the major frustrations of people affected by the disease - care is all too often fragmented and uncoordinated in response, necessitating multiple visits to hospital for example.

2017 has also seen a reorganisation of their Information and Support Services, enabling them to help even more people with PSP and CBD. Part of this work included making their Helpline the single point of contact for people affected by both conditions, while PSPA is also looking for more volunteer support workers so that they can provide local support to more people with PSP and CBD.

Prof Huw Morris is a leading PSP/CBD expert and Chief Investigator of the PROSPECT study Looking forward, 2018 looks to be a milestone year, the association will hold the first International Symposium on PSP, organised jointly with their American counterparts CurePSP - to be held at the Royal College of Physicians in October.

“Please turn up to our international research symposium,” comments Andrew “We have 300 places for researchers interested in neurodegenerative conditions – come along and see the excellent research that is being done around world to find treatments and cures for these devastating conditions.”

This symposium is to be held every two years and is one element of their broader efforts to coordinate the international response to PSP and CBD. Ultimately, they’d like to organise and participate in international research projects, working with their counterparts in Sweden, the rest of Europe and the US. PSPA is also at work developing a new strategy, the draft of which is available to view on their website now, with the opportunity for you to provide feedback. Many of the ideas incorporated into the strategy have come from the community, with over 160 ideas submitted by family friends and carers of those affected by the condition.

Fundraising efforts continue apace, with PSPA organising a virtual 5K race, an accessible event open to all, with the option to complete the race in stages – whenever you want, wherever you want over a five day period. Some willing volunteers in the PSPA office are running 1K a day in their lunch hour over five days. More fundraising events are in the pipeline, all planned with accessibility in mind.

When it comes to raising awareness, a new hard-hitting social media campaign is being created as we speak and PSPA is also working with medical students at Imperial College who are developing a range of projects to help raise awareness amongst GPs and consultants. Moving into 2019, PSPA will be celebrating 25 years since its foundation.

Research into tau proteins and tau therapies is the key to developing treatment for PSP and CBD, and such work is likely to provide fresh insights into Alzheimer’s and Parkinson’s too. So to funding decision makers everywhere one can’t help but ask – why would you not be investing in research that could herald such a medical breakthrough?

Why would you not fund research into diseases that are amongst the most devastating from which a person can suffer?

Prof James Rowe (Cambridge Uni), a leading PSP/CBD expert and leading the imaging arm of the PROSPECT study

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www.pspassociation.org.uk

| nafic |

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Campus is well placed as Northern bioeconomy prepares for strong growth The bioeconomy in the North of England stands on the cusp of signifigant expansion and one of the science parks which is ready to play its part is the National Agri-Food Innovation Campus (NAFIC).

Situated at Sand Hutton, a few miles north of the historic city of York, NAFIC sits in 80 acres of parkland and has 380,000 sqft of built space, with a range of options for organisations seeking to operate within a stimulating scientific environment.

Offering an alternative to science parks in London, Cheshire, Nottingham, Oxford and Cambridge, the site is home to sixteen science based organisations, four of them Government-backed and twelve from the private sector.

The attraction for all of them is that the campus offers not only secure and quality accommodation and associated support services to the standard required for ‘regulatory science’ , but also an atmosphere cultivated for thriving cross-disciplinary interaction with world-class scientists and businesses across all points of the life science spectrum.

It also houses the 250-seat Lakeside Conference Centre, an on-site restaurant, nursery and gym, adding to the attraction for its tenants.

CEO of anchor tenant Fera Science Ltd, Dr Andrew Swift said: “One of the big attractions is NAFIC’s location.

“City centre campuses present too many distractions, costly commutes, difficult parking and expansion possibilities. By contrast, at NAFIC we are situated in attractive and peaceful countryside, which creates an environment that is good for focus and original thinking.

“NAFIC creates an atmosphere which fosters ingenuity and ground-breaking science “This is not a university campus. It’s a space that is used by commercial organisations and so commercial confidentiality is vital, however, the assorted events, gatherings and ‘community’ that NAFIC establishes encourages scientists to ‘bump into each other’ from which inventive relationships are built and great ideas are born.”

The success of the approach taken by the team at NAFIC is plain to see, with 87 per cent occupancy and opportunities

36

EIGHT HUNDRED PEOPLE ARE EMPLOYED ON THE SITE AND IN THE PAST 12 MONTHS, THREE OF ITS SMALLEST SMES HAVE ALL DOUBLED IN THE SPACE THEY OCCUPY ON SITE.

| BIOSCIENCE TODAY SPRING 2018 |

| nafic |

The potential for growth is there and not just in the food sector. Life sciences covers a wide range of areas and we are working to support organisations large and small to develop their ideas.

Andrew Swift Science Director

to further develop its available space, including for pilot and demonstrator plants.

revolutionise how farmers manage crop threats including pests and diseases.

Eight hundred people are employed on the site and in the past 12 months, three of its smallest SMEs have all doubled in size and space.

The Centre’s consortium partners include Bayer CropScience, Frontier Agriculture, Tesco, Stockbridge Technology Centre, ADHB, CABI, Cranfield University, Fera, Newcastle and Cranfield Universities and Rothamsted Research.

Such growth fits well with the recently published Science and Innovation Audit Report: The Bioeconomy in the North of England, commissioned by the Department for Business, Energy, Industry and Skills (BEIS) as part of the research in to Britain’s Industrial Strategy and published by the University of York.

The report identified the potential to double the size of the bioeconomy in the North of England in GVA terms from £12.5 billion now to £25 billion in 2030.

CHAP enables these organisations to work together to tackle the Government’s ‘Grand Challenges’ which confront UK agri-food industry in order to raise its productivity and international competitiveness.

Andrew Swift

OPPORTUNITIES IDENTIFIED IN THE REPORT INCLUDE: n Making the transition in the chemicals industry to become significantly bio-based n Academic collaborations with major global companies and encouraging more large companies to pursue open innovation n Supporting disruptive innovators to thrive in the region and bring new products and services to market n Supporting food and feed processing industries to establish competitive advantage in bioeconomy products.

Andrew added: “I am confident that the life sciences sector in the north of England can grow in the years to come.

If you look at the food industry as an example, we have a corridor stretching from fishing ports at Grimsby to Liverpool in which can be found a wide range of companies, everything from food processors and canneries to game producers.

“The potential for growth is there and not just in the food sector. Life sciences covers a wide range of areas and we are working to support organisations large and small to develop their ideas.

“NAFIC deals in knowledge and its transfer; a great example of this is an innovation voucher scheme called: Stimulating Innovation in the Agri-Food Sector (SIAFS) which Fera offers in cooperation with Make it York, the organisation responsible for developing business growth in the city.

Andrew is confident that the campus will continue to grow by attracting more organisations who seek to innovate in a secure, creative and knowledge-rich environment.

“Life sciences is not just about the big names. Very often when a big company announces a new development, it started with work done by a small organisation and the campus serves both.”

He said: “NAFIC has proved itself very popular and the past year has been a strong one, with a lot of interest in what it can offer, including its latest concept in supporting transient or interim research and development needs via a ‘Research Hotel’ model.

Among large organisations with which SMEs can work on the campus are a number of nationally important centres which have created their headquarters at Sand Hutton.

“NAFIC is not just looking for large companies. It welcomes and works well with smaller businesses and those seeking incubation.”

This includes The Centre for Crop Health and Protection (CHAP) – a £21.3 million government funded investment to

www.nafic.co.uk

37

| salmonella |

| BIOSCIENCE TODAY SPRING 2018 |

Unlocking the secrets of a

killer Scientists are making significant progress to improve the testing and treatment of the killer illness salmonella.

Achieving success is vital because every year almost one in ten people fall ill to food-borne illnesses, with many of them dying, according to the World Health Organisation (WHO).

According to the WHO, diarrhoeal diseases are the most common of the illnesses resulting from unsafe food with 550 million people falling ill each year, including 220 million children under the age of five years, and salmonella is the cause in a quarter of the cases.

Salmonella is a ubiquitous and hardy bacteria that can survive several weeks in a dry environment and several months in water, making it particularly resilient.

Now, a new test developed by American researchers has been developed which allows accurate and rapid testing for the bacteria.

The breakthrough could have wide-raging applications because salmonella can infect animals as well as people, with commonly reported cases of people falling sick after handling pets and livestock.

The new method, first developed for automated food safety testing then adapted by Cornell University scientists for a wider range of sample types, can detect the bacteria from samples including swabs, feces, milk and blood.

Tests to confirm the presence of the bacteria used to take days but, thanks to the new technique, they can take 24 hours, with a hundredfold improvement in detection for

at least one type of Salmonella, called Salmonella Dublin, which is difficult to grow in culture, making diagnosis difficult.

Salmonella Dublin is ‘host-adapted’ in cattle, meaning that infected animals can become permanent or long-term carriers, putting herds, especially susceptible calves, at risk.

The strain can infect people who may be exposed by contact with infected animals, by drinking raw milk, or by consuming other contaminated food products. It has higher hospitalisation and fatality rates than other Salmonella types, causing infection of body tissues, similar to typhoid.

Belinda Thompson, assistant clinical professor at Cornell’s Animal Health Diagnostic Center and a senior author of the paper outlining the research, said: “Because we have this 24-hour turnaround time with the new test, there are veterinary hospitals and clinics that can test and get results rapidly and make sure they are not exposing other animals to Salmonella. Fast clinical diagnoses also allow veterinarians to quickly quarantine an infected animal.”

Work on the test was funded and developed in collaboration with the Food and Drug Administration (FDA) Veterinary Laboratory Investigation and Response Network. Cornell works closely with FDA scientists to evaluate and perform new methods that the government agency can share with other veterinary labs.

38

| BIOSCIENCE TODAY SPRING 2018 |

| salmonella |

Research deepens understanding of salmonella Understanding the way salmonella works is crucial for vets and doctors alike and now techniques created by scientists at the Norwich Research Park in the UK are helping to uncover what makes certain strains of bacteria more dangerous than others.

There are many different types of salmonella bacteria, most of which have adapted to live in the guts of different animals, including humans, other mammals and birds, and some of these strains have further evolved extra abilities to evade their hosts’ immune defences. These types of salmonella are of most concern as they cause the most severe disease, including typhoid.

To understand what makes certain strains so invasive, researchers have been looking at the genetic differences between these and less invasive strains.

Dr TamĂĄs KorcsmĂĄros, a systems biologist from the Quadram Institute (QI) and the Earlham Institute, has led the development of SalmoNet alongside a research group at QI with expertise in salmonella infection, led by Dr Rob Kingsley.

As part of the work, Professor Jozsef Baranyi used network biology and bioinformatic techniques to collate molecular interactions within salmonella, and to link information on how genes and metabolic pathways are regulated and how proteins interact with each other.

The results of the work are being used to find out how bacteria adapt to their environment and how the disease evolves, the first time that this type of approach has been used to investigate salmonella.

Team members hope that the work may help identify potential drug targets, and help in the development of new therapies against systemic salmonella infections.

The research was supported by BBSRC.

39

| advertorial |

| BIOSCIENCE TODAY SPRING 2018 |

Nasal sprays – Key insights for a successful device development to achieve bioequivalence requirements An observation of generics in the nasal spray market will reveal to the keen observer an opportunity. Whilst the overall nasal spray market is currently experiencing limited growth, the market share of generics is increasing at a much faster rate. Seeing this, Nemera has established a unique approach for developing devices in this field. This approach follows seven steps: 1. Understand the market and identify the best reference nasal sprays to target.

2. Appraise the regulation and, by isolating the most stringent requirements, use it to drive the programme.

3. Establish the identity of the device (e.g. bill of materials, performance, patient use) using a supply of the reference from different markets.

4. Develop the device, based on Nemera’s pump platform, to have equivalent performance to the reference device with the reference drug formulation.

5. Test the performance, comparing the Nemera device with the reference with iso-formulation in a comprehensive study, to demonstrate bioequivalence.

6. Prepare the “datapack” containing robust statistical analysis to be delivered to the client, the data therein being used simultaneously to support the drug registration process and justify the device selection.

7. Repeat the study with the final drug.

UNDERSTANDING THE MARKET Over half of the topical nasal preparations market is for corticosteroids, due to the fact that they remain the frontline treatment for moderate to severe allergic rhinitis as the most effective option for relieving nasal symptoms.

The second thing to note is that the entire topical nasal formulations market is growing and evolving.

There are two key trends that can be observed as driving this evolution: the increasing competition from generics and the established brands shifting from a prescription-only to an over-the-counter (OTC) model.

Such trends are to be expected in a mature market and contribute to steady growth. However, the generics market will increase significantly. As such Nemera has selected a number of corticosteroids as part of their bioequivalence program.

APPRAISING THE REGULATION When looking at ICS as a global market it is important not to underestimate the complexity of the regulatory landscape. Across the world there are several co-existing regulatory ecosystems, each with a different approach to bioequivalence: • US FDA is the most frequently mentioned, often considered to have the most stringent regulation.

• EU regulation has the nuance that each member country may have a different interpretation of the regulations and directives.

Reference

Test

Final drug

DATAPACK Figure 1: Nemera’s device is compared to the reference with isoformulation, in a comprehensive study to demonstrate bioequivalence, before testing with the final drug.

• China CFDA regulation is still very much under construction, even if the aim seems to be to synchronize with the US FDA. As Nemera focuses on the most stringent regulation during development, here we shall use the FDA as the exemplar for how Nemera supports the registration process. Under FDA guidelines, whatever the regulatory position of the targeted reference product (i.e. prescription only or OTC not under monograph), a generic product will follow the same process for its first submission and must therefore answer to the same requirements. When modifying the dossier, that is to say when making a variation upon the first submission (e.g. to add a second source), there are two ways to go about it. The first is to repeat the same process as the first submission and the second is to use a simple equivalence of performances of the pumps, thereby bypassing the need to follow the full guidance on bioequivalence for generics.

When going through the process of registering a generic however, it may be more relevant for authorities to compare the variation directly to the reference product. That is why it is important to test bioequivalence directly from the original reference product. Thanks to its deep experience with these processes, Nemera can strongly support a submission document with the chapters linked to the device.

ESTABLISH THE IDENTITY In simple terms, a nasal spray is the combination of two regulated products, a drug and a device, which together make the combination product. Nemera’s expertise is in the latter of these two, the spray device, but it remains crucial to acknowledge throughout the design process that the device is part of the greater combination product. The device is a major contributor to treatment efficacy, patient safety and robustness of the combination product.

40

| BIOSCIENCE TODAY SPRING 2018 |

| advertorial |

Figure 2: Velocity profile of fluid passing through the nozzle, showing the swirl motion

Nemera performs studies to ensure that the three main functions of device performance are under control at all stages of development: • Preserving drug product integrity • Delivering an exact preset dose

Figure 3: CFD representation of fluid break-up as it exits a nasal device.

Nemera approaches this complex development process with multiple tools: • Experimental testing and a database of results helps track input and performance data as well as aiding in the analysis of influencing factors and trends.

• The capacity to manufacture fully functional, novel nozzles in a matter of weeks, including metrology control, enables the exploration of the design space and shorter tuning loops.

• Delivering drug product to the targeted site

DEVELOP THE DEVICE The discussion of device identity invariably brings us to the spray, which in point of fact is the hardest aspect to control, thus it is spray generation where the greatest effort must be expended during development of the device. With this in mind, let’s turn to the heart of a nasal spray device: the pump. The pump has multiple functions, one previously touched upon is metering, ensuring the delivery of a preset dose.

Another primary function of the pump is to generate a flow and, furthermore, control flow rate and pressure level to master the generation of the spray. The flow rate and pressure profiles are dependent upon the pump technology and the actuation profile, with the nominal dose of the pump also having influence due to its impact on spray duration.

Moving from heart to head, the next key part of the device to focus on in development is the nozzle, which is surprisingly complex. Inside a nozzle tip are several vertical channels which then enter into convergent channels to move the rising liquid into a swirl chamber before exiting through the orifice at the tip of the nozzle. It is noteworthy how small the dimensions of all these parts are, typically in the range of 0.2-0.4 mm, especially given the complex geometry. As such, high precision manufacturing is required to ensure that the final combination product generates a consistent spray after scale-up to industrial manufacture.

The spray forms the basis for analyzing how well and how consistently the device will deliver drug product inside the nasal cavity. These droplets, and hence the spray, are hugely impacted by the viscosity, and to a slightly lesser extent the surface tension, of the drug formulation. Batch-to-batch variability of viscosity can be significant and must be taken into account when designing a spray with a defined target as is the case in the bioequivalence approach. Because the impact of viscosity is so tremendous, the factors that affect viscosity, such as temperature, the delay between actuations and the fluid memory effect (i.e. whether or not the product has been shaken), must in turn be considered.

41

• Computational fluid dynamics (CFD) modelling allows for a richer understanding of the physics involved. CFD can also be used to run sensitivity analysis on specific parameters, as seen earlier in this article.

• Finally, mathematical modelling makes the link between input variables and output performance.

Understanding the sensitivity of the performance in the design space allows the set-up of control strategies, ensuring robust and controlled performance when it comes to mass production. And, by incorporating data analysis and mathematical modelling into development, Nemera achieves acute refinement of the design, all building to one ultimate goal: to have the spray on target.

TESTING THE PERFORMANCE Nemera has developed its own testing laboratory using cutting-edge technology.

Customized testing methods are used to cover all aspects of a nasal device from broad parameters (dosage accuracy, leakage, weight loss, etc) to in-depth spray characterization (droplet size distribution, spray pattern, plume geometry).

Tests are also performed on the component materials to establish extractable profiles. All of which can be customized to the needs of clients and partners.

CONCLUSION Nemera brings great benefits to partners looking to develop a generic nasal spray, a process far more complex and involved than it may first appear, but which growing market demand worldwide shows is increasingly likely to be a worthwhile endeavor. Able to offer expertise in market understanding, regulatory affairs, device development and statistical analysis, Nemera also prides itself on being a cooperative, committed and responsive device design partner. www.nemera.net

| what is life? |

| BIOSCIENCE TODAY SPRING 2018 |

what is Professor Gideon Lowy and P A Cook Edited by Michael Woods

In 1943, the quantum physicist Erwin Schrödinger stood up in Trinity College Dublin and delivered what might be described as the biggest scientific disappointment of the century. His work on quantum mechanics, which so beautifully explained the nature of matter, failed to explain the material workings of a cell. We are made from nothing more than the elements in the Periodic Table, and this leads to the most fundamental question in science; “How do elements change into living things, and ultimately, us?”

As Abbott, Davis, Pati write in Quantum Aspects of Life, “To be sure, quantum mechanics is indispensable for explaining the shapes, sizes and chemical affinities of biological molecules. From the point of view of fundamental physics however, life remains deeply mysterious. Life still seems an almost magical state of matter; furthermore, its origins from non-living chemicals is not understood at all.” (Imperial College Press, 2008) Our proposition is that the mystery is not so mysterious after all. The problem is a systemic misinterpretation of reality. It lies not in the verified findings of generations of brilliant scientists, but in Western scientific dogma and tradition. It lies in the traditional scientific perspective, that the universe works according to the laws of cause and effect, and that there must always be an underlying physical cause of every action. Western scientific tradition dictates that the laws of physics must underpin everything we observe.

It is our interpretation of the data that has prevented us from being able to describe ‘life’ scientifically. We have good mathematical models for the chaotic, complex and self-organizing behavior of matter, but the models have nothing to do with the fundamental laws of physics. This is true at the atomic and gravitational scales, and we have not connected the two, because they are studied in different university departments.

In 1687, Newton found that the predictable laws of physics only worked for two bodies in space. Worse still, in 1887 Poincaré wrote a mathematical proof showing there are no equations which could predict the motions of three equal size bodies in space. In his theory of General Relativity from 1916, Einstein asks us to see distortions of space as the reason the Earth moves around the Sun, where bodies in space are ‘forced’ to follow mathematical curves, and only collide if the curves meet: there is no ‘physical’ attraction.

Likewise, magnetic and electrical fields have no physical part. As physicists Julian Schwinger and Michael Faraday have pointed out, fields are a property of space – and space has no physical structure, only mathematical properties.

Simple actions in nature can be described by the mathematics of traditional physics; and complex actions, of the same physical components, can be described by the mathematics of chaos and complexity. Mathematics is the only realm of science which is self consistent and describes everything. The axioms in Euclid’s Elements are as true today as when they were written 2300 years ago.

Mathematical Proofs are absolute, and Poincare’s proof that there are no equations from physics to predict the motion of three bodies in space, means that the fundamental laws of physics can never be used to explain the chaotic, complex or self-organizing behavior of matter in the Solar System.

 Continues on page 38

42

| BIOSCIENCE TODAY SPRING 2018 |

| what is life? |

life?

Since the 1970s, computers have been used to reveal a hidden world which no scientist could ever have predicted: the laws of chaos theory.

This has been treated as a fringe science, but it shows up universally in the behavior of all matter. Mechanical oscillators, electrical circuits, lasers, beating hearts, chemical reactions, nerve cells, heated fluids and many other systems, all show the same quantifiable chaotic behavior.

43

| what is life? |

Continued from page 37

| BIOSCIENCE TODAY SPRING 2018 |



Mathematics describes the structure and behavior of all matter; atomic, gravitational, simple, complex, predictable, unpredictable, living and nonliving.

This gives us an explanation why, • Molecules obediently line up according to the mathematical rules of group theory, as the physicist Eugene Wigner puzzled over in his essay “The Unreasonable Effectiveness of Mathematics in the Natural Sciences.”

• The Fibonacci Sequence, and the Golden Ratio, appear in physical structure – living and nonliving – but not in physics books.

• Logarithmic spirals and fractals appear in the physical structure of galaxies, typhoons, plants and animals, but never in physics books.

• Genetics is driven by the mathematics of the HardyWeinberg Law. • Population growth models come from chaos theory and produce the same logistic maps as chaos in an electrical circuit or turbulence in a fluid.

• Equations can be taken straight out of economics, and applied to animal behavior.

• Light moves in a sine wave, a mathematical function, not a physical one.

• Units of electrical energy come in positive and negative forms, mathematical, not physical aspects of matter.

• The gaps between prime numbers and electron orbital shells show a 1:1 match.

Consequently, mathematical patterns are exactly what we would expect to see in the physical structure of nature.

Since the 1970s, computers have been used to reveal a hidden world which no scientist could ever have predicted: the laws of chaos theory. This has been treated as a fringe science, but it shows up universally in the behavior of all matter. Mechanical oscillators, electrical circuits, lasers, beating hearts, chemical reactions, nerve cells, heated fluids and many other systems, all show the same quantifiable chaotic behavior.

In his book “Chaos and Nonlinear Dynamics” Robert C Hilborn states: “The theory of nonlinear dynamics has helped us describe, organize and even quantify much complex behavior. It is this contact with experiment that leads us to believe that the current developments in nonlinear dynamics will make a lasting contribution to our

scientific world view …” and that “… the mathematical constants which underpin chaos will one day sit alongside the Fine Structure Constant and other universal numbers in physics.” (Oxford University Press, 1994) Chaos Theory is as experimentally testable, verifiable and quantifiable as physics, and Complexity Theory gives us an explanation of how self-organizing systems form. So what is the problem? Why can’t we just put physics and nonlinear dynamics together, and say we have a complete description of reality? The problem is tradition, and only tradition, a Western belief in a ‘physics only’ universe.

Reality can only be described correctly, if we use all four behavioral aspects of matter. (1) Gravitational physics, the laws and the outcomes start off deterministic, but flip over into chaotic. (2) Quantum physics, the laws start off deterministic, but flip over into probabilistic, (3) Chaos, the laws are unpredictable at the individual event, but predictable at the collective. (4) Complexity, the laws conserve and feedback information, allowing the build up of self organization and complex systems.

We can state that Life is a complex self-organizing system made of matter, which follows the simple predictable laws of physics, as well as, the complex unpredictable laws of chaos and complexity. To describe a living system or the Solar System, you need all four sets of rules. Reality is built upon cause and effect, and the causes are mathematical, not physical.

Mathematics is the base set of universal rules, and we can now put physics, chemistry, and biology together, under a common, self consistent set of laws.

Complex systems are built from common rules which, • are held together by the atomic laws, and held in place by gravitational laws • self organize, grow, evolve, and behave, according to complex nonlinear mathematical laws It is time for a disjointed and philosophically inconsistent Western tradition* to give way to a more Universal Truth.

As Sir Roger Penrose puts it: “Do we really need to move forward to radical new theories of physical reality, as I myself believe, before the more subtle issues of biology can be understood in physical terms?” *Eastern philosophy has always taken the laws of mathematics to govern the universe.

44

| BIOSCIENCE TODAY SPRING 2018 |

| what is life? |

We can state that Life is a complex self-organizing system made of matter, which follows the simple predictable laws of physics, as well as, the complex unpredictable laws of chaos and complexity. To describe a living system or the Solar System, you need all four sets of rules. Reality is built upon cause and effect, and the causes are mathematical, not physical.

45

| news |

| BIOSCIENCE TODAY SPRING 2018 |

Killer whale can mimic human speech

© Marineland

A killer whale has the ability to mimic human speech, according to researchers at the University of St Andrews. The female whale learned to “say” words such as “hello” and “bye bye” by copying a trainer at a marine park in France.

In partnership with the Complutense University of Madrid, the research team had hoped to discover whether killer whales could learn new vocalisations by imitating others.

They studied the female, named Wikie, at Marineland Aquarium in Antibes, France. Words were specifically chosen which meant nothing to her to see whether she was capable of copying new, unfamiliar sounds.

She was able to repeat words including “Amy” and “one, two, three” while partially immersed in water with her blowhole exposed to the air. Often the whale was able to produce reasonable copies on the first attempt, providing conclusive evidence that killer whales have the capability to learn new sounds.

It has long been known that killer whales in the wild have calls specific to their own pod or set of pods, and when captive killer whales are moved to a new environment they change their calls to fit in with their new companions.

But until now there was no evidence that these differing “dialects” were the result of learning.

Professor Josep Call of the School of Psychology and Neuroscience at the University of St Andrews, said: “The killer whale that we studied in captivity was capable of

learning vocalisations of other killer whales and also human vocalisations by imitating them.

“Therefore this result suggests this is also a plausible explanation for how killer whales in the wild learn the vocalisations of other killer whales and how they develop and transmit their dialects.”

Whales and dolphins are among the few mammals, other than humans, that can learn to produce a novel sound just by hearing it.

The paper, ‘Imitation of novel conspecific and human speech sounds in the killer whale (Orcinus orca)’ by Jose Z Abramson, Victoria Hernandez-Lloreda, Lino Garcia, Fernando Colmenares, Francisco Aboitiz and Josep Call is in the 31 January issue of the Proceedings of the Royal Society B [DOI: 10.1098/rspb.2017.2171].

46

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2 8 18 6

Polonium

Ununpentium

18

35.453

127.6

2 8 18 32 18 5

2 8 7

20.1797

Cl

Tellurium

Bismuth 2 8 18 32 32 18 4

rod

2 8

Ne

Chlorine

78.96

121.76

Flerovium

2 8 18 30 8 2

34

10

Fluorine

Selenium

Sb

207.2

2 8 18 32 32 18 3

2 8 18 5

2 7

18.9984032

S

Antimony 2 8 18 32 18 4

17

32.065

74.9216

Lead

Ununtrium

164.93032

Dysprosium 2 8 18 32 27 8 2

Ho

2 8 18 29 8 2

As

2 8 6

F

Sulfur

Arsenic

Tin

aluminum nanoparticles

2 8 18 25 8 2

33

118.71

Thallium 2 8 18 32 32 18 2

2 8 18 4

9

15.9994

30.973762

72.64

50

16

Phosphorus

Germanium 2 8 18 18 3

2 8 5

O

2 6

Oxygen

P

He Helium

8

14.0067

28.0855

204.3833

Mercury

15

Silicon

114.818

81

2 8 4

N

2

4.002602

2 5

Nitrogen

Si

Indium 2 8 18 32 18 2

7

12.0107

69.723

2 8 18 18 2

2 4

Carbon

Gallium

Cadmium

Gold

111

Al

Zinc

196.966569

2 8 18 32 32 17 1

14

10.811

Boron 13

65.38

Silver

Platinum 2 8 18 32 32 15 2

2 8 18 1

107.8682

2 8 18 32 17 1

2 8 3

C

26.9815386

63.546

2 8 18 18

6

Aluminum

Copper

Palladium

192.217

2 8 18 32 32 14 2

Cu

B

2 3

nanodispersions

TM

advanced polymers

tering targets

2 8 18 16 1

Iridium

single crystal silicon

rbium doped fiber optics

Rh

29

Nickel

102.9055

Europium 2 8 18 32 24 8 2

Pu

Ni

2 8 16 2

58.6934

Rhodium

151.964

Samarium 94

45

Hassium

62

Promethium 2 8 18 32 21 9 2

2 8 18 32 32 13 2

Bohrium

2 8 18 23 8 2

2 8 18 15 1

190.23

Nd Pm Sm

Neodymium

refractory metals 232.03806

61

76

28

Cobalt

Osmium

107

Seaborgium

2 8 18 22 8 2

Ru

2 8 15 2

58.933195

101.07

186.207

quantum dots 2 8 18 19 9 2

44

Rhenium 2 8 18 32 32 11 2

Co

Ruthenium 2 8 18 32 13 2

Re

27

Iron

(98.0)

183.84

106

Fe

2 8 14 2

55.845

Technetium

Tungsten 2 8 18 32 32 12 2

26

54.938045

95.96

2 8 18 32 11 2

Mn

2 8 13 2

Manganese

Molybdenum

180.9488

diamond micropowder 90

42

2 8 18 12 1

Tantalum 2 8 18 32 32 10 2

25

51.9961

92.90638

2 8 18 32 10 2

Cr

2 8 13 1

Chromium

Niobium

Hafnium

Actinium

58

2 8 18 10 2

178.48

Lanthanum 2 8 18 32 18 8 2

50.9415

Zirconium

138.90547

Barium

Fr Ra tantalum (223)

2 8 18 18 8 2

V

24

2 8 11 2

Vanadium

91.224

Yttrium

137.327

Cesium 87

88.90585

Strontium

23

Titanium

Rb Sr Y Zr rhodium sponges Rubidium

2 8 10 2

47.867

Scandium 2 8 18 8 2

5

surface functionalized nanoparticles

9.012182

Lithium

11

Be

2 2

2

dysprosium metal

99.999% ruthenium spheres

1.00794

Hydrogen

praseodymium

gadolinium acetate

ultra high purity ma

europium phosphors

platinum ink solar energy

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