Bio Science Journal 4

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BioScience BIOSCIENCE JOURNAL SPRING 2015

JOURNAL SPRING 2015

Three-parent baby technology Fantastic Remarkable breakthroughs voyage

Aiming high

BSc



BIOSCIENCE JOURNAL SPRING 2015

WELCOME z

Welcome

Time to get excited about science A

s a child I loved watching 1970s TV hit the Six Million Dollar Man, featuring a former astronaut with amazing abilities.

science at its heart is intoxicating and our teachers have to make sure that message comes through.

Steve Austin could do it all – run faster than anyone else, jump huge distances, see for miles, and all down to the bionic technologies that had rebuilt his body.

If it does, who knows what amazing breakthroughs we will see from the next generation of scientists?

To a child it was brilliant stuff, intoxicating, exciting, but it was also a bit far-fetched. Until now, that is. It has taken time but four decades later science is starting to catch up.

John Dean

Editor in chief

We are already seeing remarkable breakthroughs in robotics and in this edition of Bioscience Journal, we report on advances made in the United States which will aid those with sight loss and on work in the UK to create a hand that can sense pressure and temperature and transmit the information to the brain. Both developments are brilliant for patients, offering real hope to millions, but there is also a direct link to another of our pieces in this edition, the feature that looks at how to engage more young people in science. There is increasing concern worldwide at the low figures for young people entering the scientific professions, beguiled instead by the likes of careers in the media, and announcements like those in the US and the UK can only help to reverse that trend. Why? Because they are exciting. Yes, I know that much of science is painstaking, that it is not all glamorous breakthroughs, that most of it happens away from the public eye, but in order to hook young people we have to excite them first and foremost. We have to get the message over to them that science is important, that it makes a real difference. Our science teachers have to burn with enthusiasm for the subject, they have to make sure that young people are thrilled about science. And so must all of us with an opportunity to influence young people. All jobs have their dull elements, the chores that threaten to grind us down, sure, but

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BIOSCIENCE JOURNAL SPRING 2015


BIOSCIENCE JOURNAL SPRING 2015

CONTENTS

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14

19

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17

21

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18

24-27

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BIOSCIENCE JOURNAL SPRING 2015

CONTENTS z

Contents

3

Introduction/Foreword

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Contents

8-15

UK News

17-21

World News

24-27 Imaging Techniques

46-49

28-29

28-29 3 Person Babies 34-37 Bionics 40-45 Nanotechnology 46-49 Spectrometry 50-53 Young People in Science

Editor

John Dean john.dean@distinctivepublishing.co.uk

50-53

34-37

Design

Distinctive Publishing, Unit 6b, Floor B, Milburn House, Dean Street, Newcastle Upon Tyne NE1 1LE Tel: 0845 884 2385 www.distinctivepublishing.co.uk

Contributors

John Dean & Francis Griss john.dean@distinctivepublishing.co.uk

Advertising

Distinctive Publishing, Unit 6b, Floor B, Milburn House, Dean Street, Newcastle Upon Tyne NE1 1LE Tel: 0845 884 2343 email: john.nielson@distinctivegroup.co.uk www.distinctivepublishing.co.uk

40-45

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Distinctive Publishing or BioScience Journal 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 Journal.


BIOSCIENCE JOURNAL SPRING 2015

z NEWS

z Artists impression of an angeoplasty stent

The time for stents is here The use of stents to keep neck arteries open is just as effective as invasive neck surgery for long-term prevention of fatal and disabling strokes, according to an international trial. Now, the team says that stents should be considered as a more credible option by surgeons treating carotid artery disease. Led by University College London (UCL) and funded by the Medical Research Council and Stroke Association, the research paper was written by researchers from UCL, Basel University, Switzerland, the London School of Hygiene& Tropical Medicine, the University Medical Center Utrecht, Netherlands, Sheffield Teaching Hospitals NHS Foundation Trust, and Newcastle University. They investigated complications arising out of the way the brain’s blood supply comes from the carotid arteries, two large blood vessels that run through the neck. Carotid artery disease occurs when cholesterol and fatty deposits build up in these arteries, restricting blood flow and increasing the risk of stroke. In the UK, carotid artery disease is most commonly treated by an invasive surgical procedure called endarterectomy, which leaves a scar on the neck and can lead to heart attack, short-term facial paralysis from nerve damage, and bleeding.

Stenting is an alternative procedure in which a small mesh cylinder is used to keep the artery open and is inserted under local anaesthetic through a small nick in the groin and fed up to the neck using a thin wire. The procedure is less invasive, causing only minor bruising in the groin, no risk of nerve damage and a lower heart attack risk than endarterectomy. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for up to ten years.

Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group compared to 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life. Study leader Professor Martin Brown, from the UCL Institute of Neurology, said: “At the moment, stenting is not widely used in the UK due to historical uncertainty over its long-term effectiveness. “However, we have now shown that stenting is just as good as endarterectomy for preventing fatal and disabling strokes. “We have also shown that the risk of stroke during the procedure is no higher for stenting than for endarterectomy in younger patients. “The risks of each procedure are different and will vary depending on the patient, but stenting should be offered as an option to many more patients under the age of 70.

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“One of the issues is that there are not many centres in this country that currently offer stenting as an option so the patient choice is not there. Now that we know stenting is effective in the long term, more staff should be trained to carry out the procedure and gain experience. “Otherwise there is a vicious cycle where nobody at a centre has stenting experience so patients are only offered endarterectomy and staff cannot learn or observe the procedure. In other countries, stenting is more widespread and the safety of the procedure improves as staff gain experience.” Dr Shamim Quadir, Research Communications Manager at the Stroke Association, said: “A transient ischaemic attack, also known as a mini-stroke, can be a warning sign that someone has carotid artery stenosis, and is at risk of having a major stroke. Preventative procedures to treat such carotid artery stenosis are therefore crucial. “Carotid endarterectomy is a common, yet invasive surgery used to treat carotid artery stenosis, and is widely used throughout the UK. Previously, far less was known about the long-term effectiveness of stenting as an alternative procedure. “These latest research findings suggest that overall, stenting is just as safe, and equally effective for the long-term prevention of fatal and disabling strokes. Both procedures carry their own risks, and these will need to be considered for each individual patient. “


BIOSCIENCE JOURNAL SPRING 2015

NEWS z

New information on molecule

Scientists have cast new light on what allows some cases of Ductal Carcinoma in Situ (DCIS), a non-invasive form of breast cancer, to resist treatment Researchers from The University of Manchester and University Hospital of South Manchester NHS Foundation Trust investigated the role of the molecule FAK in controlling the resistance of DCIS to radiation. The team found that blocking the activity of FAK reduces the growth of breast cancer stem cells and improves sensitivity to radiotherapy.

z Vince Cable opens Virology Institute

Animal disease laboratories are officially opened Business Secretary Vince Cable has officially opened the BBSRC National Virology Centre, a containment laboratory based at The Pirbright Institute in Surrey. The £135m laboratories have been developed to strengthen the UK’s ability to prevent and control virus diseases of livestock and viruses that spread from animals to people. Funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the laboratory uses bio-containment technologies developed for The Pirbright Institute to allow scientists to study diseases such as bluetongue, foot-and-mouth disease, avian influenza and African swine fever. The new centre will help them to predict and prevent outbreaks and develop vaccines and diagnostics Mr Cable, said: “Disease spreading from animals to humans isn’t a plot from a Hollywood movie. Its results can have devastating impact on our health and the health of the countryside economy. This new centre will help protect both.” Professor John Fazakerley, Director, The Pirbright Institute, said: “Our new high-containment facilities have an exceptionally high standard of design and finish and will allow us to retain and recruit the very best expertise and continue to deliver high-impact science.

Immune system boosted

Scientists have developed a new method of boosting the ageing immune system. Early tests in mice show that the compound allows the immune system to mount a more powerful protective response following vaccination. The compound, called spermidine, is now being developed by the researchers at the Medical Research Council Human Immunology Unit at Oxford University as a potential drug to make vaccines more effective in the elderly.

“The impact of the Institute’s science is global, its facilities and expertise provide a national capability and its work makes a strong contribution to health and economic prosperity in the UK and worldwide.” Professor Jackie Hunter, BBSRC Chief Executive, said: “In an era of global trade and climate change the UK cannot rely on its island status to protect us and cutting-edge science and facilities are vital to safeguard against these threats.” There is evidence that the approach works as scientists increasingly understand the way such diseases function. For example, BBSRC-funded scientists at Pirbright saved the nation an estimated £480m and protected 10,000 jobs in the rural economy during the last bluetongue outbreak through their forecasting of the threat posed by the disease. Pirbright research and surveillance was also used to eradicate rinderpest - a disease that devastated European cattle herds in the early modern period and which until recently destroyed livelihoods and caused great animal welfare problems in Africa. The Institute’s research regularly brings forward new vaccines and diagnostics in partnership with commercial companies.

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New cancer drug

University of Manchester scientists have shown that a new drug inhibits the growth of tumours in the laboratory. Their work suggests that the AstraZeneca drug AZD3965 could be a new cancer treatment. The team looked at small cell lung cancer cells and Professor Ian Stratford, who led the research, said: “This drug is currently being tested in clinical trials as a single agent, and we’ve shown that combining this drug with radiotherapy could offer a new treatment approach for cancer patients.”


BIOSCIENCE JOURNAL SPRING 2015

z NEWS

Cost has to be a factor in vaccination programme

University researchers say that there needs to be a realistic approach to the cost of a meningitis vaccination programme. In March 2014, the Joint Committee on Vaccination and Immunisation (JCVI), the expert group that advises UK governments on vaccination, recommended that Bexsero be offered to babies at two, four and 12 months of age as long as the Department of Health can obtain it at a cost-effective price. Bexsero is the first vaccine to broadly protect against meningitis B but the research now suggests the Government would need to negotiate a considerable reduction in the list price in order to provide the same value for money as other programmes in the NHS. Researchers at the Universities of Bristol, Cambridge and the London School of Hygiene and Tropical Medicine conducted a modelling study to estimate the potential impact of a vaccine on cases of meningitis

and septicaemia and the cost-effectiveness of immunisation programmes. The model took into account factors including how many cases could be averted, the cost of care, litigation costs, the quality of life for those left with disabilities and the impact on families. Dr Hannah Christensen, who led the research at the University of Bristol, said: “Our study suggests vaccinating babies, who are most at risk of meningococcal disease, would have the greatest immediate effect on reducing cases. “After taking into account comments raised by stakeholders following the interim JCVI decision, our research shows that offering the vaccine to infants could be cost-effective, but given the current evidence the vaccine price would need to be quite low to achieve this.”

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The model estimates that 1,447 cases of all meningococcal disease and 59 deaths occur annually in the absence of vaccination against group B meningococcal disease. Cases would be cut by 26% in the first five years if the recommended vaccination programme at two four and 12 months is followed. This could be cost-effective with the vaccine priced at a lower amount per dose, say the team. Maximum reduction will be achieved by combining infant vaccination with an adolescent vaccination at 13-years-old. This could see annual cases reduced by 49% in 10 years and 60% in 20 years.


BIOSCIENCE JOURNAL SPRING 2015

NEWS z

Postgraduates are honoured

Six Bristol University postgraduates have been awarded prizes for the exceptional quality of their research degree theses in the academic year 2012/13. They included in the medical and biosciences field William Razzell in the School of Biochemistry for his study of wound inflammation and Dr Neil Uptal Barua in the School of Clinical Sciences for his work into drug delivery for Alzheimer’s Disease.

Stigma ‘hampers research’

Can games encourage children to learn science? A project, investigating whether the uncertainty inherent in games can increase the rate at which children learn science is under way after a £650,000 award.

Academics from the University of Bristol will work with schools in the area to build on existing knowledge of how games, including video games, engage the brain’s reward system. It’s one of six new projects funded by the Wellcome Trust and the Education Endowment Foundation to investigate a variety of ways neuroscience might improve teaching and learning in the UK. Teachers often encourage their students by giving rewards, such as gold stars, in return for good answers. In this project, the rewards for good answers are decided by chance. Dr Paul Howard-Jones, from the Graduate School of Education at the University of Bristol, who is leading researchers at Bristol and Manchester Metropolitan University, said: “Previous research has shown that not

knowing whether a reward will materialise can add to the excitement and motivation around learning.

“We’re gaining a better understanding of how uncertainty can increase the rate at which we learn, thanks to new insights that have arisen from neuroscience. We’re really looking forward to working with teachers to develop a novel game-based approach to whole-class teaching that applies these insights.” Working with students in Year 8 science lessons, classes will collaborate in teams to accumulate points by answering questions, with the option of doubling or losing points for correct answers on the spin of a wheel of fortune. Free web-based technology will be used to connect the class up and allow all students to participate at once. The technology will also randomly select teams for special challenges, and provide occasional pay-outs of points based purely on luck. Researchers are initially looking to work with six schools in the South West, starting in January 2015, to help develop the gaming experience. The project will then be rolled out more widely to include 35 schools in the area. Researchers are especially keen to work with schools who have an above-average intake of disadvantaged students.

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The stigma surrounding dementia is a barrier to early diagnosis, care and research into the disease, according to a report. It says that people over 55 fear being diagnosed with dementia more than any other condition and at least one in four hide their diagnosis, citing stigma. The report has been published by think tank International Longevity Centre UK with the Medical Research Council, Alzheimer’s Research UK and the Alzheimer’s Society, supported by the drug company Pfizer.

Funding boost for research

A partnership led by the Medical Research Council will invest more than £230 million in technologies aimed at identifying the causes of diseases such as cancer and dementia. The technologies will examine how differences in the cellular and molecular make-up of people affect how they respond to diseases. The Clinical Research Infrastructure Initiative brings together funding from the UK Government, devolved administrations, Arthritis Research UK, British Heart Foundation, the Wellcome Trust and Cancer Research UK for 23 projects.


BIOSCIENCE JOURNAL SPRING 2015

z NEWS

Funding announced for drug development Cambridge-based Bicycle Therapeutics has secured an equity financing of £20 ($32M) million which will allow for the clinical development of therapeutic bicycle drug candidates in oncology. The funding will allow the company to press ahead with work which could bring forward new treatments not just in oncology but in other areas as well. Bicycle, a biotherapeutics company developing bicyclic peptides, has been developing its proprietary technology to discover a new class of drug candidates which have similar potency to antibodies but are 100-fold smaller and can be manufactured using simple economicallyviable chemical synthesis. The new financing will support the clinical development of bicycle-drug conjugates (BDCs) that are highly selective to tumour-specific targets with sub-nanomolar affinities. Preclinical models show that the BDCs extravasate and penetrate tissues much more rapidly and efficiently than antibodies, which leads to the rapid death of cells. This results in effective tumour lysis with minimal systemic exposure.

Bicycle technology has broad applicability in areas including oncology, respiratory, inflammatory and ophthalmology diseases.

The company’s projects in BDCs for oncology will be leveraged through a series of partnerships. The first partnership, with ThromboGenics, is developing bicyclic peptide drug candidates to a specific ophthalmology target for the treatment of diseases such as diabetic macular edema. Andrew Sandham, Chairman of Bicycle, said the latest funding was important because it allowed the company to press ahead with developments. He said: “This second round financing enables us to advance our BDC candidates to clinical development in cancer indications. “We also have the capacity to work collaboratively with pharma partners on other targets and indications in many diseases.” Bicycle’s technology is based on the work performed at the MRC Laboratory of Molecular Biology in Cambridge by the scientific founders of the company, Professor Christian Heinis and Sir Gregory Winter. The company is funded by Atlas Venture Novartis Venture Fund SVLS SR One and Astellas Venture Management.

This second round financing enables us to advance our BDC candidates to clinical development in cancer indications. We also have the capacity to work collaboratively with pharma partners on other targets and indications in many diseases. Andrew Sandham Chairman of Bicycle

The rising cost of alcohol-related hospital admissions The number of alcoholrelated NHS admissions reached almost 10 million in England during 201213, according to recentlypublished statistics. A total of 9.9million admissions were reported in findings taken from Alcohol Concern’s Alcohol Harm Map with accident and emergency accounting for six in every ten alcohol-related hospital visits. However, inpatient admissions were responsible for almost two thirds of the total cost incurred.

The new Alcohol Harm Map also shows that:9.6 million people in England are now drinking in excess of Government guidelines of whom 2.4 million are classed as high risk The cost of inpatient admissions partly attributable to alcohol was £1.3bn almost 3 times greater than the cost of those which were wholly attributable (£518m) There was a £708m cost to the NHS for hypertensive disease inpatient admissions attributable to alcohol consumption alone Alcohol is attributable for almost half of all head and neck cancer inpatient admissions at a cost to the NHS of £65.3m Just over 13% of all malignant neoplasm of breast inpatient admissions were attributable to alcohol at a cost to the NHS of £27.1m

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Alcohol Concern Chief Executive Jackie Ballard said: “The NHS is now facing an intolerable strain from alcohol-related illnesses. “This is not just from readily-identifiable causes such as A&E visits and admissions for liver disease but from a significant number of other conditions in which alcohol plays a major but often underappreciated part. “We need to ensure adequate alcohol care pathways are prioritised and appropriate services are put in place to ease this burden. However we also urgently need action to prevent alcohol misuse; the first and most effective of which is for the government to implement a minimum unit price which has the potential to save the economy millions and most importantly save lives.”


BIOSCIENCE JOURNAL SPRING 2015

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BIOSCIENCE JOURNAL SPRING 2015

z NEWS

Athletes’ poor oral health a concern It’s one of medicine’s strange anomalies. International athletes may be fitter than most people on the planet but many of them suffer from poor oral health.

The event happened on the back of a UCL survey at the London 2012 Olympic Games that found that 18% of athletes said that their oral health had a negative impact on their performance and 46.5% had not been to the dentist in the past year.

Now researchers say that the problem, which affects athletes’ general health, needs to be tackled.

“Professional athletes and their teams spend a lot of time and money on ways to marginally improve performance, as this can make all the difference in elite sports.

The group, led by University College London health experts, say that despite education programmes the situation shows little sign of improvement. Ina joint statement published in the British Journal of Sports Medicine, the authors call for action to tackle poor oral health among athletes. They say that simple measures such as encouraging better brushing and flossing could provide the marginal performance gains that are similar to expensive physical therapies. The statement came out of the Oral Health and Performance in Sport collaboration in April 2014, led by Professor Ian Needleman of the UCL Eastman Dental Institute and Professor Fares Haddad of the Institute of Sport Exercise and Health (ISEH). This resulted in a conference held at UCL where experts in oral health and sports medicine met with sporting associations and elite athletes.

Professor Needham said: “Oral health could be an easy win for athletes, as the oral conditions that can affect performance are all easily preventable.

“Simple strategies to prevent oral health problems can offer marginal performance gains that require little to no additional time or money. “Things like better tooth brushing techniques and higher fluoride toothpastes could prevent the toothache and associated sleeping and training difficulties that can make the crucial difference between gold and silver.” The team believe that part of the problem is the intense dietary and training pressures on athletes, which could put them at high risk of oral health problems. For instance, saliva helps to protect teeth from decay and erosion, so dehydration and drying of the mouth could increase the risk of oral health problems. The amount of energy that athletes need for training often means they have highcarbohydrate diets and regularly use sugary, acidic energy drinks. These may contribute to decay and erosion in athletes’ teeth.

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Professor Needham said: “We do not want to demonise energy drinks and are not saying that athletes shouldn’t be using them. “However, people should be aware of the risks to oral health and can take simple measures to mitigate these. “For example, water or hypotonic drinks are likely to be more suitable for simple hydration, and spit don’t rinse after tooth brushing. For sports where athletes need a lot of energy drinks, high fluoride toothpastes and mouthrinses should be seriously considered.” The authors also recommend regular dental appointments to identify and address oral health issues before they can affect performance. Olympic athletes are all supposed to have a dental check-up within 12 months of the competition but, as the previous survey found, almost half of the athletes London 2012 had not. The joint statement calls for national sport funders and policy organisations to take the lead in ensuring that oral health is regularly assessed, especially pre-season, to allow for personalisation of prevention plans and early treatment of any disease. Dr Mike Loosemoore, Lead Consultant in Sport and Exercise Medicine at the Institute of Sport, Exercise and Health, said: “I think this is an important consensus statement. My experience of instituting a programme of improving oral health in elite sportsman has had a very positive effect.”


BIOSCIENCE JOURNAL SPRING 2015

NEWS z

Drs. Scott Webster and Anna Williams

Charity in the news

Sky News presenter Dermot Murnaghan took time out of his schedule to try his hand at trading the markets for two charities including children’s charity Action Medical Research. He was taking part in Celebrity Trader, an online financial trading challenge for City Index which sees a different celebrity each month trying to make as much profit as possible for the charity of their choice. The presenter raised in the region of £4,000.

Getting the word out

Research offers hope for MS sufferers University of Edinburgh scientists are working with biotechnology company Genzyme on drug discovery research that could reduce neuron damage in the brain. The collaboration - supported by Edinburgh BioQuarter’s Business Development team - will seek to identify therapies capable of reducing neurodegeneration, mostly in cases of Multiple Sclerosis (MS). MS is caused by damage to myelin, the protective layer that surrounds nerve fibres. The damage affects the transmission of electrical signals from the brain to the rest of the body and results in problems with muscle movement, balance and vision. A natural process called remyelination can repair damaged myelin and restore nerve function but is inefficient in MS.

Now, scientists from the University of Edinburgh have discovered a naturallyoccurring molecule that prevents the cells needed to help repair damaged myelin from reaching the area of damage. By working with Genzyme, co-investigators Dr Anna Williams, of the MRC Centre for Regenerative Medicine, and Dr Scott Webster hope to identify inhibitors of the molecule to encourage the cells to reach the damaged area. Dr Williams said: “If successful, this will be a step-change in MS treatment as current treatments are unable to repair the damaged neurons that cause the symptoms of MS. “Ultimately, this could reduce neurodegeneration in MS and the accumulation of disability in patients. This treatment could also be used in other diseases where myelin is damaged, such as spinal cord injury.” Dr Johanne Kaplan, Vice President of Neuroimmunology Research at Genzyme,said: “Remyelination-promoting therapies remain an unmet need and would be of great benefit to MS patients.”

“We buy and sell used lab equipment” www.lvscientific.com Email: rob@lvscientific.com 15

A booklet outlining the way complementary therapies can help Parkinson’s Disease sufferers was commended at the British Medical Association Information Awards. The awards celebrate the production and distribution of clinically balanced information and it is the fourth year in a row where resources produced by the charity Parkinson’s UK our resources have been recognised.

Awards announced

The Biotechnology and Biological Sciences Research Council (BBSRC) has recognised outstanding contributions to bioscience made by four of its research community. Three awards will be presented to individuals who have accomplished significant advances in bioscience research and one award will recognise excellence in bioscience communication. Those honoured are: Professor Caroline Dean, John Innes Centre

Professor Dame Linda Partridge, University College London Professor Jeff Errington, Newcastle University Professor Russell Foster, University of Oxford


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BIOSCIENCE JOURNAL SPRING 2015

WORLD NEWS z

Plant-based solution could ease suffering A humble plant could offer hope for people at risk of pulmonary hypertension. Researchers at the University of Pennsylvania (Penn) and the University of Florida in the United States have identified a drug that can be used to treat those suffering from the condition, for which few therapy options exist. The medicine is grown in the leaves of plants from Penn’s greenhouse. The team says that in patients with pulmonary hypertension, the arteries of the lungs become constricted, which increases the workload on right side of the heart to pump blood through the lungs. Over time, the right chamber of the heart, which usually is small, becomes enlarged and dysfunctional. Currently, the most successful drugs for the disease cost tens of thousands of dollars. That could change according to the researchers on the study, for whom the senior author of the study was Henry Daniell, professor of biochemistry and pathology and director of translational research at Penn’s School of Dental Medicine. Fellow Penn Dental Medicine authors included postdoctoral associate Kwang ChulKwon and research assistants Shina Lin and Guiying Jin. The Penn team collaborated with researchers from the University of Florida, including Vinayak Shenoy, an assistant research scientist in the College of Pharmacy Department of Pharmacodynamics; co-senior author Mohan Raizada, a distinguished professor of physiology and functional genomics in the Evelyn F.

and William L. McKnight Brain Institute; and Michael Katovich, a professor in the College of Pharmacy. Vinavak Shenoy said: “Pulmonary hypertension is relatively a rare disease. It’s been neglected by the industry so there aren’t many drugs out there. “The first drug for pulmonary hypertension was approved in 1995, although the disease was known since the early 1900s.” Mohan Raizada said that blood pressure is regulated by a hormonal system called the renin-angiotensin system. Too much of a key hormone in this system, angiotensin II, can raise blood pressure. However, angiotensin II is balanced by two other hormones , ACE 2 and Ang-(1-7), that maintain normal cardiopulmonary pressure, according to previous research. The research has shown that increasing the amount of these hormones in the body prevents pulmonary hypertension. Because the hormones are already found in the human body, they had little concern about potential side effects. Mohan Raizad said: “All of the drugs on the market so far for hypertension and cardiovascular diseases are based on inhibiting angiotensin II and aren’t very effective. “Many years ago, we began to question why the prevalence of hypertension and cardiopulmonary diseases does not decrease when you inhibit angiotensin II. Instead, we thought we should be targeting the hormones that balance angiotensin II.” Prof Daniell said: “The proteins we were dealing with are very large and unstable, only lasting

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a few minutes in the bloodstream when given as an injection, “We needed to find a way to stabilise the proteins to increase their lifespan in the bloodstream and make sure it was working the way we wanted it to.” When patients are treated with other medications, they typically see only a slight improvement — about a 10% reduction in pulmonary pressure. After the rats with established pulmonary hypertension had been treated with the medication for two weeks, their pulmonary pressure was reduced by 20%. After four weeks of using the plant-delivered medication to treat a group of 8-10 rats with pulmonary hypertension, the researchers found that the medication reduced pulmonary pressure by 32%. Vinavak Shenony said that, although pulmonary hypertension causes vessels in the lungs to constrict, patients actually die from heart failure. However, the drug improved function on the right side of the heart, potentially avoiding heart failure in patients. The researchers now hope to test the drug in clinical trials and Mohan Raizada said: “The bottom line is that we have been able to find a revolutionary way to deliver a therapy through oral delivery for a disease which is in critical need for an immediate innovative therapy.” The study was funded by the National Heart Lung and Blood Institute, National Institutes of Health and American Heart Association.


BIOSCIENCE JOURNAL SPRING 2015

z WORLD NEWS

Collaboration announced

The HudsonAlpha Institute for Biotechnology and The University of Alabama in Huntsville, both in America, have joined together to strengthen the business skills of life science sector start-ups in the area. The HudsonAlpha-University of Alabama in Huntsville Entrepreneurship Collaboration will improve the educational experience for students linked to both organisations. HudsonApha is a non-profit research institute working in genomic research, educational outreach and economic development.

Study will examine impact of medical marijuana A $500,000 gift from international best-selling author and mental health advocate Patricia Cornwell is funding research in America into the impact of medical marijuana. McLean Hospital and Harvard Medical School researchers will explore the potential impact of medical marijuana on cognition, brain structure and function. The Marijuana Investigations for Neuroscientific Discovery (MIND) Program, will also gauge study participants’ perceptions of their own quality of life as it relates to medical marijuana treatment. Patricia Cornwell said: “We are seeing the country’s view on marijuana shift dramatically and now is the time to allow science to inform our policies and our decisions.,” The author, who is a member of McLean Hospital’s National Council and was presented with the hospital’s highest honour in 2012 for her mental health advocacy, added: “The MIND Program has the potential to revolutionise what we know about medical marijuana and what we think we know.” Researchers in the team say that, despite the move toward the legalisation of medical marijuana, with 23 states and the District of Columbia legalising its use, no published studies to date have assessed its potential impact on cognition and brain function. Lead investigator Staci Gruber, PhD, director of the Cognitive and Clinical Neuroimaging Core at McLean Hospital and associate professor of Psychiatry at Harvard Medical School, said: “At this point, policy has vastly outpaced science, with little empirical data available regarding the impact of medical marijuana on cognitive function, despite the legal status of the product in a growing number of states.

“Findings from this investigation will ultimately foster a greater understanding of the impact of medical marijuana on cognitive function and brain structure, and may in turn facilitate the examination of the efficacy of marijuana for the different disorders for which it is prescribed.” Because marijuana is difficult to standardise and highly variable, the majority of current research studies investigate the potential therapeutic properties of cannabinoid chemicals delivered in standardised pharmaceuticals that have not yet reached the market. Also, none so far have included an assessment of neuropsychological performance before, during and after treatment. As a result, there is a gap in the knowledge between ongoing medical marijuana research, the products currently available to the public and their relationship to cognitive function, say the team. Staci Gruber said: “Given the considerable difficulty with cognitive function and disrupted mood experienced by patients with severe medical disorders, the addition of marijuana, which has shown promise in alleviating a range of symptoms, could potentially improve cognitive performance. “Equally critical, data showing a loss or impairment of cognitive function following the use of medical marijuana could inform alternative courses of treatment and prevent unjustified exposure to harm, especially in vulnerable populations.” The initial phase of the MIND Program is expected to last two years, with the expectation of extending the investigation to include clinical trials and additional areas of research.

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Lab recognised

Alltech Inc’s Analytical Services Laboratory has been awarded ISO/ IEC 17025:2005 accreditation, an international standard that recognises the competence of testing laboratories. The laboratory in Ireland opened in September 2012 and is a division of Alltech, a global leader in improving the health and performance of people, animals and plants. Within the last two years, more than 5,000 feed and feedstuff samples from more than 50 countries have been analysed by the lab.

Gas could treat trauma conditions Researchers in the United States say that xenon gas, used for anaesthesia and diagnostic imaging, could treat post-traumatic stress disorder (PTSD) and other memory-related disorders.

Edward G. Meloni, PhD, assistant psychologist at McLean Hospital and an assistant professor of Psychiatry at Harvard Medical School, said the study found that xenon gas can reduce memories of traumatic events. He said: “It’s an exciting breakthrough as this has the potential to be a new treatment for individuals suffering from PTSD.”

Xenon gas glowing


BIOSCIENCE JOURNAL SPRING 2015

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Findings offer hope in the battle against cancer German researchers have confirmed that the risk of developing bowel cancer can be reduced by adopting some or all of five key healthy lifestyle changes. Scientists at the German Institute of Human Nutrition Potsdam-Rehbruecke found that the greater number of healthy behaviours a person adopts, the greater chance they have of avoiding the disease. The five lifestyle choices highlighted are: taking regular exercise; maintaining a healthy weight; not smoking; limiting alcohol consumption and eating a balanced diet. More than half (55%) of bowel cancer cases occur in the developed world, such as North America and Western Europe. Previous research has highlighted a link between Western lifestyles and cancer rates. This 12-year study, part of the wider European Prospective Investigation on Cancer and Nutrition (link is external) (EPIC) study, looked at the data of 347,237 men and women from ten nations, recording 3,759 bowel cancer cases. Participants were assigned one point for each of the five behaviours they adopted, or zero if they didn’t adopt any of them, adding up to a cumulative score. Those who combined two healthy behaviours saw their risk lowered by 13 per cent, rising to 21 per cent for those with three healthy behaviours, 34 per cent for those practising four and 37 per cent for those who adopted all five. Lead author Krasimira Aleksandrova said the findings show that more than one in five of male cases and about one in ten female cases could have been prevented if everyone adopted all five healthy behaviours.

Welcoming the research, Fiona Osgun, health information officer at Cancer Research UK, said: “We know that there are lots of things you can do to reduce the risk of bowel cancer, including being more active, keeping a healthy weight, not smoking, cutting down on alcohol and eating a healthy balanced diet. “This large study reiterates what other studies have shown - that the effects add up - so the more of these lifestyle factors you adopt, the lower the risk of bowel cancer. “It’s great to see research that is reaffirming that when it comes to reducing your cancer risk an all-round approach to a healthy lifestyle is best.” * In a separate development, US scientists have developed a new computer-based method of analysing biological data and used it to unearth

the genetic roots of an aggressive form of brain cancer known as ‘mesenchymal’ glioblastoma. Columbia University Medical Center researchers combined the new method, or ‘algorithm’, with traditional computer models to look at the underlying causes of a form of glioblastoma in 250 patients. The algorithm called DIGGIT (Driver-Gene Inference by Genetical-Genomic Information Theory) identified that about half of the tumours were caused by the loss of a gene called KLHL9. By reintroducing the protein that is usually created by a functioning KLHL9 gene into mice with the disease, the scientists found they were able to shrink tumours, highlighting a new potential strategy to treat the disease.

Could arthritis drugs help kidney transplant survival? A research programme is under way in America that could see drugs used for arthritis also being used to help kidney transplant patients.

The University College of San Francisco (UCSF) is the lead institution on a seven-year, $17 million study funded by the National Institutes of Health. Its aim is to determine if immune system cells and/or a drug now used for treating rheumatoid arthritis can be effective in improving and maintaining the long-term health of transplant recipients. Although acute rejection rates are down to less than 15% and one-year graft survival up to more than 90%, long-term graft success rates have remained unchanged. A major

contributor is progression of interstitial fibrosis and tubular atrophy in the kidney.

The cells that the researchers are focused on are regulatory T cells (Tregs), which are a small population of lymphocytes that suppress the activity of other immune cells. They maintain normal immune system homeostasis and safeguard against autoimmune diseases, and their immunosuppressive properties also can be harnessed to control transplant rejection. Leading the study is principal investigator Dr Flavio Vincenti, UCSF professor of medicine and a kidney and pancreas transplant specialist at UCSF Medical Center. Other participating institutions are the University of Alabama at Birmingham, Emory University and Cedars-Sinai Medical Center.

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Dr Vincenti said: “This grant allows us to work toward achieving two important advances in the transplant field. “We can introduce personalised medicine by treating patients based on molecular profiling of their kidney. We also can allow control of the response to the transplant by the patients’ own immune systems by regulatory T cells, either through infusions or pharmacologically.” Researchers believe inflammation can be controlled in kidney transplant recipients by increasing the number or activity of Tregs, either by infusing them into the body or by blocking interleukin 6 (IL6) with the drug tocilizumab. To test this, they will conduct clinical trials.


BIOSCIENCE JOURNAL SPRING 2015

z WORLD NEWS

Understanding sudden deaths

Researchers in America have captured images of complex proteins thought to be at fault in some cases of sudden cardiac death. The images secured by a team at Johns Hopkins University School of Medicine reveal the connection between some genetic mutations and electrical abnormalities of the heart, deepening understanding of the causes of the fatal attacks.

China expansion

Posterior mediastinal mass : unknown diagnosis

Study provides better understanding of oesophagal tumours Researchers in Australia have cast new light on the factors that trigger a third of oesophageal tumours, the fastest rising cancer in the country. The Queensland team have identified sudden “chromosomal catastrophes” and will now carry out work to discover what triggers the events. The study involved scientists from QIMR Berghofer Medical Research Institute, The University of Queensland (UQ) School of Medicine and UQ’s Institute for Molecular Bioscience (IMB). Dr Nic Waddell, who co-led the study, said the research was based on genome-wide sequencing of 22 patients with oesophageal adenocarcinoma (OAC) from three Brisbane hospitals. He said: “In 32% of patients there had been a catastrophic event that damaged the DNA which resulted in highly mutated and rearranged genomes, and we confirmed this finding in another 101 patients.

“In all patients there was evidence of genetic scarring or ‘footprints’ of damage to the DNA in the tumour cells. “These findings have given us an important clue as to how these tumours might have eventuated.” Dr Andrew Barbour, of UQ School of Medicine, said OAC had one of the poorest outlooks of all solid tumours, with only 14 per cent of patients surviving five years. He said: “Removing the tumour is their best hope, but fewer than 50% of patients are diagnosed early enough for surgery.” The team says that the most significant risk factor was the pre-malignant lesion known as Barrett’s oesophagus. Patients with Barrett’s are routinely monitored for development of malignant tumours but reflux, smoking and obesity are other risk factors, and men account for eight in every nine OAC cases. Dr Barbour said: “The number of patients diagnosed with oesophageal cancer has doubled in the past 20 years and is expected to double again in the next two decades.” The study was funded by the NHMRC and follows a study by Australia’s major OAC scientists in a Centre of Research Excellence at QIMR Berghofer, where Dr Waddell is now based.

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US firm Akers Biosciences, a designer and manufacturer of rapid diagnostic screening and testing products, has signed a Joint Venture Agreement with Hainan Savy Investment Management Ltd. The deal means that they will research, develop, produce and sell Akers’ products in China. The Joint Venture Company will be located in Haikou, the capital city of the province of Hainan, China, and is incorporated as Hainan Savy Akers Biosciences, Ltd.

Pioneering scientists receive awards

Horizon has announced that two scientists working on one of its projects have received Breakthrough Prizes. The prizes, created two years ago, went to Dr Emmanuelle Charpentier, a member of Horizon’s Scientific Advisory Board, and Dr Jennifer Doudna at a ceremony in California, United States. Together they worked on unravelling the mystery of a microbial defence mechanism called Crispr/Cas9 that protects bacteria from invading viruses.

Accolade for professor

Professor Adele Green, a skin cancer expert in Australia, has been named Person of the Year by Brisbane magazine bmag. Professor Green heads up the Cancer and Population Studies Group at QIMR Berghofer Medical Research Institute and has worked in skin cancer and melanoma research for more than 20 years. She was the first to establish the role sunscreen plays in the prevention of skin cancer.


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Tracing the origins of HIV pandemic It has always been known that the HIV pandemic began in Africa but there was little to say where it originated. Until now.

An international team, led by scientists from Oxford University in the UK and the University of Leuven in The Netherlands has reconstructed the genetic history of the HIV-1 group M pandemic, the event that saw HIV spread across the African continent and around the world. They have concluded that it is almost certain to have begun its global spread from Kinshasa, the capital of the Democratic Republic of the Congo (DRC). The findings suggests that the common ancestor of group M is highly likely to have emerged in Kinshasa around 1920, based on 95% of estimated dates between 1909 and 1930. HIV has been transmitted from primates and apes to humans at least 13 times but only one of these transmission events has led to a human pandemic, resulting in almost 75 million infections to date. The team’s analysis suggests that, between the 1920s and 1950s, a ‘perfect storm’ of factors, including urban growth, strong railway links during Belgian colonial rule, and changes to the sex trade, saw HIV emerge from Kinshasa and spread across the globe. Professor Oliver Pybus, of Oxford University’s Department of Zoology, a senior author of the

paper, said: “Until now, most studies have taken a piecemeal approach to HIV’s genetic history, looking at particular HIV genomes in particular locations. “For the first time, we have analysed all the available evidence using the latest phylogeographic techniques, which enable us to statistically estimate where a virus comes from. “This means we can say with a high degree of certainty where and when the HIV pandemic originated. It seems a combination of factors in Kinshasa in the early 20th Century created a perfect storm for the emergence of HIV, leading to a generalised epidemic with unstoppable momentum that unrolled across sub-Saharan Africa.” Professor Philippe Lemey, of the University of Leuven’s Rega Institute, another senior author of the paper, said: “Once the pandemic’s spatiotemporal origins were clear, they could be compared with historical data and it became evident that the early spread of HIV-1 from Kinshasa to other population centres followed predictable patterns.“ Dr Nuno Faria, of Oxford University’s Department of Zoology, first author of the paper, said: “‘Data from colonial archives tells us that by the end of 1940s over one million people were travelling through Kinshasa on the railways each year. “Our genetic data tells us that HIV very quickly spread across the Democratic Republic of the Congo, travelling with people along railways and waterways to reach Mbuji-Mayi and Lubumbashi in the extreme South and Kisangani in the far North by the end of the 1930s and early 1950s.

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“This helped establish early secondary foci of HIV-1 transmission in regions that were well connected to southern and eastern African countries. We think it is likely that the social changes around the independence in 1960 saw the virus break out from small groups of infected people to infect the wider population and eventually the world.“ The team suggests that social changes such as the changing behaviour of sex workers and public health initiatives against other diseases that led to the unsafe use of needles may have contributed to turning HIV into a full-blown epidemic. This supports ideas originally put forward by study co-author Jacques Pepin from the Université de Sherbrooke, Canada. Professor Pybus said: “Our research suggests that following the original animal to human transmission of the virus, probably through the hunting or handling of bush meat, there was only a small window during the Belgian colonial era for this particular strain of HIV to emerge and spread into a pandemic. “By the 1960s transport systems, such as the railways, that enabled the virus to spread vast distances were less active, but by that time the seeds of the pandemic were already sown across Africa and beyond.“ The team says that more research is needed to understand the role different social factors may have played in the origins of the HIV pandemic.


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BIOSCIENCE JOURNAL SPRING 2015

ADVERTORIAL

The Enemy Within – getting the paperwork right

The Scottish Business Resilience Centre conference on The Enemy Within in Edinburgh on 12th February will cover many ways of protecting your business however there are some basic but often overlooked ways to help protect your business from leakage of valuable information. Most people are honest but may be careless or misunderstand the consequences of discussing certain business issues and this can be a particular issue with staff coming from academia or a different industry with different practices. It is worthwhile having a formal induction process for new staff in which you explain the company’s confidentiality procedures. Understanding why not everyone is granted access to every piece of company information and the need for a planned

release of information tends to ensure greater compliance and care. Regular staff meetings therafter ensure people engage with the company and its goals. Staff and consultancy contracts and shareholder agreements in small companies usually contain confidentiality clauses but do not forget your non executive directors (NEDS). All confidentiality clauses involving individuals who may visit your site should cover not just materials deliberately handed to them but also information obtained visually on your premises. Senior staff and directors may have obligations to the company implied by law but these may not be as extensive as you might expect so if you want to be safe spell out what you feel is appropriate for your business in a service contract. You might also consider a clause allowing immediate termination if a NED takes on a project or directorship with a potential competior. Take care with investment agreements that have wide exceptions to the usual non disclosure obligations – you need to consider how you handle these situations. You should be looking at how you communicate with NEDS and consultants and in particular the security of the electronic systems that they use. Do you include their security policies when you conduct pre

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engagement audits of a consultant or other collaborator? Are your own computer back ups secure? How are sensitive documents stored and accessed. If you have a “need to know” policy does that mean disclosure only to those who need it to do their job or does it include everyone of a particular seniority. What about their secretaries? If you exchange information under a CDA with a collaborator do you have a detailed list of what has been sent or received? How do you manage this material and the associated relationship? Finally it is useful when staff leave to conduct an exit interview to remind them of their continuing obligations and to recover all company material from their possession. Garden leave is another useful tool if permitted by contract to keep departing staff away from the latest company developments. If they are joining a competitor a letter to the competitor advising them of the employee’s on going obligations and requesting that they are not put in a compromising position may also act as both a reminder and a deterrent..

By Patricia Barclay Bonaccord


BIOSCIENCE JOURNAL SPRING 2015

z FEATURE

In the picture For many years, research into dementia has thrown up as many questions as it has answers. Now, a new project is seeking to change that and at its heart lies the rapidly-advancing science of imaging technology. Medical imaging technology has revolutionised health care over the past 30 years, developing at a staggering rate and allowing medical practitioners to see detail inside the body that was never available to them before. Imaging technologies that are routinely used include conventional X-Ray, molecular imaging, which is used in nuclear medicine, magnetic resonance imaging (MRI), ultrasound imaging, which uses highfrequency sound waves to produce images of soft tissue and internal body organs, and Positron Emission Tomography (PET), which is used to produce detailed threedimensional images of the inside of the body.

The result has been that doctors have been able to detect disease much earlier and researchers can build up a better picture of the workings of the body. It is that potential that is driving the new research into dementias.

According to Dr Ross Maxwell, one of the medical experts involved, the project will use imaging technology to look deep into the brain to better understand changes that may be associated with the early stages of dementia.

So far, much of the work involving imaging has tended to focus on cancers but now the same technologies are being used on other conditions and among projects making use of the advances is the recently-launched Dementias Platform UK (DPUK), led by the Medical Research Council in the UK.

To do that, PET/MRI scanners will be installed at Cambridge, Edinburgh, ICL, Manchester and Newcastle universities.

The MRC is providing £12m for an initial period of five years, supplemented by £4m from six partner companies and £37m from clinical research funding announced by Chancellor George Osborne in October 2014. Among those taking part are the universities of Cambridge, Edinburgh, Imperial College London, Oxford, Newcastle, University College London and Swansea, plus contributions from Cardiff, Manchester and Bristol. DPUK’s aims are early detection, improved treatment and ultimately, prevention, of dementias, which affect more than 600,000 people in the UK alone.

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Dr Maxwell, Director of the PET Facility at Newcastle, said: “So far, imaging technologies have mainly been used in the field of cancer research, helping to develop new drugs by better understanding the effect that they are having on patients. “However, the technology can also be used to research other conditions, including dementias, which is the focus of this project. “Just as researchers are increasingly focusing on sub-categories of cancer - we have learned that there is not just one type of any cancer - so there are different types of dementia. “This project will allow us to use imaging technologies to see changes in the brain which may lead to the development of markers which allow earlier detection of dementia and which will also allow for the development of drugs to treat the condition.


BIOSCIENCE JOURNAL SPRING 2015

“We will be able to assess what stage a patient’s Alzheimer’s has reached, for example. It has become clear that there is not just one treatment for a condition and by telling us what stage a patient’s condition has reached, the imaging technology will allow us to better target treatments.” To carry out the work, the DPUK, which is in its very early stages, is creating the world’s largest study in dementias research, bringing together two million participants aged 50 and over, from 22 existing study groups within the UK. Included are people from the general population, people known to be at-risk of developing dementia, and people diagnosed with early-stage dementia. Researchers will use the information gleaned from imaging technology to look not just at the brain but also at the wider body because emerging evidence has

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linked the development of dementia with inflammatory, cardiovascular and metabolic disorders. Dr Maxwell, who is based at the Newcastle Magnetic Resonance Centre, part of Newcastle University’s Campus for Ageing Vitality, said: “The technologies that we will use, including Positron Emission Tomography and MRI, have been around for some time but the way we are putting them together to investigate dementia makes the work cutting edge.

using imaging technology to look at the role of glucose in cancers, for example, already informs our knowledge of dementia because we are looking at changes in the brain in both cases. “This work is important because with an ageing population, we need to better understand how dementias work. Imaging can help us do this.”

“This is a long-term project but it shows that something is being done to tackle dementias. It is a start and work already carried out at Newcastle is improving our understanding of dementias so can feed into the project. “What we are seeing is researchers bringing together skills from different fields. Research

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z FEATURE

Imaging technology teaches researchers about DNA changes Across the Pond, imaging technology is also shedding light on the way that environmental factors affect DNA and trigger illnesses such as cancer and lung disease.

The link has long been known but what was less clear was the mechanics by which this happened. However, now researchers at the National Institutes of Health in America (NIEHS) have found that the biological machinery that builds DNA can also insert molecules into the DNA strand that is damaged as a result of environmental factors such as ultraviolet exposure, diet, and chemical compounds in paints, plastics, and other consumer products.

strand. Time time-lapse crystallography, which takes snapshots of biochemical reactions occurring in cells, gave the team a unique view of the process. Their work showed that, after the DNA polymerase inserts a damaged nucleotide into DNA, the damaged nucleotide is unable to bond with its undamaged partner, which interferes with the repair function and ultimately leading to several human diseases. As with the UK dementias project, the information provided by the imaging technology used by NIEHS could have far-reaching implications Samuel Wilson, M.D, senior NIEHS researcher on the team, said: “No one had actually seen

how the polymerase did it or understood the downstream implications. The damaged nucleotide site is akin to a missing plank in a train track. When the engine hits it, the train jumps the track and all of the box cars collide.” Understanding that could lead to new treatments, according to Bret Freudenthal, Ph.D., postdoctoral fellow in the group. Bret said: “One of the characteristics of cancer cells is that they tend to have more oxidative stress than normal cells. Cancer cells address the issue by using an enzyme that removes oxidized nucleotides that otherwise would be inserted into the genome by DNA polymerases. Research performed by other groups determined if you inhibit this enzyme, you can preferentially kill cancer cells.”

Understanding how this happens is important because these damaged molecules trigger cell death that can lead to cancer, diabetes, hypertension, cardiovascular and lung disease, and Alzheimer’s disease. It was an example of the benefits to be gleaned from advances in imaging techniques. In the case of the work carried out at NIEHS, the technique used was on time-lapse crystallography. The imaging technology allowed researchers to determine that DNA polymerase, the enzyme responsible for assembling the nucleotides or building blocks of DNA, incorporates nucleotides with a specific kind of damage into the DNA

• Representative coronal T1-­weighted scans in a patient with Alzheimers disease (right), a patient with Dementia with Lewy Bodies (middle) and an age matched healthy person (left). • The scans reveal increase brain atrophy in both the Alzheimers Disease (AD) and Dementia with Lewy Bodies (DLB) subject compared to control, particularly in the enlarged sulcal spaces. • Hippocampal atrophy (arrowed) is clearly seen in the AD patient, while the DLB subject and control appear similar. • Hippocampal atrophy on MRI is a clinical measure used in the evaluation and diagnosis of AD. Healthy DLB AD Magnetic Resonance Imaging (MRI) These data are from the work funded by the Sir Jules Thorn Charitable Trust through their Biomedical Research Award

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Why the new technology is so exciting A key feature in imaging technology is that it provides truly simultaneous imaging of anatomy, physiology and function (from MRI) and of molecular targets (from PET).

The standard configuration in PET-CT joins two scanners together, end-toend. Typically, a CT scan is done first and then the patient bed is moved automatically into the PET gantry. In that case, the decay (positron emission) of an isotope such as 18F is detected following an anti-matter : matter annihilation.

• Representative Arterial Spin Labeling (ASL) scans where intensity shows cerebral blood flow (upper panel) and the equivalent T2-­weighted FLAIR scans highlighting anatomy and periventricular white matter change in a patient with Alzheimers disease (left) compared to an age matched healthy person (right). • The FLAIR scan clearly reveal atrophy with loss of temporal lobe tissue and enlarged ventricle. The ASL blood flow maps show posterior hypoperfusion in the patient.

The positron collides with an electron, mass is converted to energy and the two resulting gamma rays trigger scintillation crystals surrounding the patient. PET-MR scanners have the scintillation crystals embedded in the central section of the magnet so that PET measurements can be done throughout the MR imaging examination. This has presented technical challenges in the devices and materials that can be used. Photomultiplier tubes amplify signals in PET-CT but are not compatible with powerful magnetic fields, so have been replaced by avalanche photodiodes. The material used to make MR detectors can attenuate gamma rays and the absence of CT (X-ray imaging) makes this more difficult to correct. Apart from the ability to make structural and molecular biology based measurements in patients at exactly the same time (to be exploited by informatics approaches), MRI will be valuable in correcting PET imaging for motion. This will apply in body imaging, to deal with breathing and heart movements, but also in the brain, where experience shows that even control subjects find it difficult to avoid head movements, let alone those patients who may also have movement disorders. On a more practical level, the combination of PET and MRI measurements into a single examination will have a lower radiation exposure, be easier to schedule into treatment studies and more convenient for patients.

PET scan showing high uptake and wide distribution of 18FAmyvid in the brain of 'subject A' in a dementia imaging study

PET scan showing low uptake and limited distribution of 18FAmyvid in the brain of 'subject B' in a dementia imaging study

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z FEATURE

Three-parent baby technology clears final hurdle When science is at its best, it pushes the boundaries of what is possible and makes us think about the big questions. Even if the issues it raises are deeply uncomfortable. That has certainly been the case with the debate in the UK over what have been dubbed ‘three parent babies’, where ethical beliefs have collided with strong scientific evidence. The idea of using genetic material from a second mother to create a baby has evoked passionate reactions from supporters and opponents alike, prompted by the pioneering work of Newcastle University scientists seeking to protect babies from serious inherited mitochondrial diseases.

Known as ‘mitochondrial donation’, the techniques involves removing faulty mitochondria inherited from the mother and replacing them with the healthy mitochondria of another woman. The baby’s nuclear DNA, containing 99.9% of genetic material from the mother and father, remains unchanged but the procedure has still proved controversial and the debate has gone far beyond the basic science.

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z FEATURE

Nevertheless, having weighed up evidence for and against, Peers sitting in the House of Lords in February approved historic legislation which would see Britain take advantage of the work by becoming the first country in the world to create three-parent babies, despite fears that children could be born sterile. The vote came after Health Minister Lord Howe urged Lords to pass an amendment to the 2008 Human Fertilisation and Embryology Act which would permit the controversial IVF techniques aimed at preventing the diseases. The decision, taken first by MPs then backed by the Lords, enables the Human Fertilisation and Embrology Authority (HFEA)to consider granting licences to use the new IVFbased technique developed by scientists at the Wellcome Trust Centre for Mitochondrial Research at Newcastle University. Although the three-parent baby technique could save lives, opponents, including church leaders and pro-life groups, have warned that the change has been brought about too hastily and paves the way for designer babies. In the Lords debate, for example, Lord Deben called for a delay and asked Peers to form a committee to look at the safety and legality of the procedure. He warned that children born from the technique could be sterile and argued that the majority of the public did not agree with the procedure. Former Attorney General Baroness Scotland also said the legislation had been rushed through but Lord Howe, dismissing the concerns, said that mitochondrial replacement could ‘give real hope to families’. He said: “It would be cruel and perverse to deny them that opportunity for any longer than necessary.” Lord Winston, one of Britain’s leading fertility experts, also backed the law, saying: “ And Chief Medical Officer Professor Dame Sally Davies said: “It would give these women their own children and these families hope, and I believe this is right. “We have a very strong regulatory system that would regulate first the service and secondly would review every individual case before they could happen.” Scientists at Newcastle University have welcomed the news that politicians have voted for a change in the law.

Professor Doug Turnbull, Professor of Neurology and a consultant at Newcastle Hospitals NHS Foundation Trust, Newcastle University, said: “This is wonderful news for patients and families affected by mitochondrial disease. “Mitochondrial donation has undergone essential scientific, ethical and parliamentary scrutiny. I am delighted that the House of Lords supported the regulations with such enthusiasm.” Mitochondrial diseases are caused by inherited mutations in the DNA contained in mitochondria – tiny structures present in every cell that generate energy. Every year, about one in 6,500 children are born with severe mitochondrial diseases, which can be devastating and particularly affect tissues that have high energy demands – brain, muscle (including heart), liver and kidney and can also lead to death in early infancy. Professor Alison Murdoch, Head of Newcastle Fertility Centre at Life, part of the Newcastle Hospitals NHS Foundation Trust, said: “For 10 years we have publically discussed mitochondrial donation to explain how it could help patients whose families are blighted by the consequences of mitochondrial abnormalities. “Whilst acknowledging the views of those who have a fundamental objection to our work, Parliament has determined that we should continue. We hope that opponents will accept its democratic decision. “ “The science will be reviewed and, if accepted, we hope to be able to submit a treatment application to the HFEA when regulatory policies have been determined.“ Behind it all lies true human tragedy. One mother who knows first hand about the devastating effects is Sharon Bernardi, who lost all seven of her children to mitochondrial disease. She said of the breakthrough: ”This is the best thing in the world that could have happened. It is such good news for affected families, like winning the lottery a thousand time over. “Professor Turnbull has known me and my family for many years and I believe that being part of our story spurred him on.”

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For 10 years we have publically discussed mitochondrial donation to explain how it could help patients whose families are blighted by the consequences of mitochondrial abnormalities. Whilst acknowledging the views of those who have a fundamental objection to our work, Parliament has determined that we should continue. We hope that opponents will accept its democratic decision. The science will be reviewed and, if accepted, we hope to be able to submit a treatment application to the HFEA when regulatory policies have been determined.

Professor Alison Murdoch Head of Newcastle Fertility Centre at Life


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BIOSCIENCE JOURNAL SPRING 2015

ADVERTORIAL

Controlling Temperature with BioPharma Dynamics BioPharma Dynamics discuss the importance of controlling parameters in your process. Temperature monitoring and control devices are an integral part of any laboratory within the pharmaceutical sector. Having a quality temperature control system in place can impact the safety and effectiveness of an end product, along with keeping running costs low and avoiding process control issues.

difference to results. The sizing of the correct temperature control equipment in your process can help in Quality By Design systems by firstly ensuring the controls maintain process quality, and secondly by highlighting any areas where there may be a process problem. Even with accurate control your system may see temperatures outside of the determined parameters due to other equipment failure; in this case, the temperature control unit can be used to sound alarms for manual intervention or feed out to other equipment for automatic adjustments.

However many people still underestimate the importance of having an adequate monitor in place, and when looking to replace chillers in a system, simply replace the old temperature control unit with the same size and type, or for new applications, utilise existing equipment on site – this can lead to unnecessarily high running costs and reduced equipment life cycle.

Temperature control is not just about cooling. Some applications such as maintaining process parameters in a Bio-Reactor may need cooling and heating capabilities within the same batch, and so some temperature control units are available to cover heat loads of exothermic and endothermic requirements. As a company focused on providing complete, cost effective results with market leading technologies, BioPharma Dynamics are pleased to be able to offer the most popular product ranges and market leading technologies. By controlling the automation of a process through SciLog systems and pumps with the temperature control units of SMC, a complete control solution is delivered including valves, pumps and chillers. This type of solution would give temperature, pressure, flow, and diagnostic control to your process at various scales. The HRS Series temperature controller range gives some excellent features to the end user with real benefits without the large cost implications. We often hear that space is at a premium in many laboratories; the compact footprint, lightweight design and the ability

In the Life Sciences industry, small fluctuations in process temperature can make a large

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ADVERTORIAL

When it comes to replacing a unit, there are some factors to be considered: Have the process parameters changed? Has the process itself changed? New equipment and pipe lengths added or valves fitted can have an impact. Was the original chiller sized to the specification of the process at the time it was fitted? to site the unit close to side panels and walls minimizes the floor space taken by the HRS, leaving valuable space for other processes. The units are available in air cooled and water cooled options with temperature stability of +/- 0.1˚C and a temperature range from 5˚C to 40˚C, ensuring processes are maintained within tight parameters and the same unit can be used on different applications. Thanks to the HRS thermo chiller’s advanced control functions, abnormalities and errors are quickly detected before any real danger can occur. When used in conjunction with other innovative products from the SMC range – such as our unique digital flow switch with integrated temperature sensor from Series PF3W or our high performance Series VX fluid valve range – we can provide with a one-stopshop service to help you automate your process. Support of the SMC temperature control product range can be guaranteed globally with 400 sales offices across 82 countries worldwide, which allows for easy tech transfer for end users or simple product support on OEM packages.

BioPharma Dynamics are a provider of solutions for traditional and single-use processed within the Life Sciences Industry. The company sees partnership with its suppliers and customers as the best way to help enhance process innovations and challenges in a positive way.

Can new technologies offer me more precise and/ or more energy efficient temperature control?

Enjoying partnerships with world leading companies such as Saint Gobain Performance Plastics, SMC Pneumatics, Colder Products, Parker SciLog and Quattrowflow Pumps allows BioPharma Dynamics to offer radical solutions with products ranging from single-use tube and sampling sets through to full process control, integrating pumps, sensors, chillers and valves.

Would more automation and monitoring in our process improve results and free up time?

For more information, contact BioPharma Dynamics on 01235 750690 or email info@biopharmadynamics.com

With a strong background in automation and partnerships with world leading innovative manufacturers, BioPharma Dynamics are able to work with you to specify the best temperature control unit to meet your process requirements. If you are looking for a no obligation survey of your systems, an informal discussion on temperature control requirements or to trial a temperature control unit in your process, then contact BioPharma Dynamics today.

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Can my supplier offer a scalable solution from lab through to pilot scale and full production?


BIOSCIENCE JOURNAL SPRING 2015

z FEATURE

Remarkable breakthroughs

that herald the age of bionics He was one of the television hits of the 1970s, the Six Million Dollar Man with his super-enhanced vision and reconstructed bionic limbs that that allowed him to run at incredible speeds and jump huge distances. It was all science fiction but, four decades later, the fantasy is starting to become reality as science comes up with ever more advanced ways of tackling physical infirmity. The Six Million Dollar Man was an American television series about a former astronaut, Steve Austin played by Lee Majors, who was given bionic implants after a terrible accident. The show, based on Martin Caidin’s novel Cyborg, ran for five seasons from 1974 to 1978 and spawned several movies. It was all very far-fetched but science has been taking the idea and developing its own version.

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Take advances made in San Jose, California, in the United States as an example, where scientists have developed a system that aids those with sight loss (one of the Bionic Man’s enhancements was incredible vision).

and Rockwell Collins, described the system as ‘a huge leap’ forward for people with age-related macular degeneration, which is the leading cause of blindness among older adults in the Western world.

The latest system, using contact lenses and eyeglasses, is controlled by the eyes: a wink of the right eye zooms in and a wink of the left eye zooms out.

Meanwhile, work is under way in the UK on another facet of the Bionic Man, this time a hand that can sense pressure and temperature and transmit the information to the brain.

The technology relies on contact lenses that contain tiny aluminum telescopes that interact with a pair of eyeglasses to move between normal and 3x magnification.

The £1.4m research project led by Newcastle University and involving experts from the universities of Leeds, Essex, Keele, Southampton and Imperial College London, aims to develop electronic devices that connect to the forearm neural networks to allow twoway communications with the brain.

The telescopes were first developed with Defense Advanced Research Projects Agency funding as super-thin cameras for aerial drones but they were adapted as an aid for people with age-related macular degeneration, the loss of light receptors on the inner surface of the eye that blurs the centre of the visual field. Now, optical engineer Eric Tremblay of the Swiss Federal Institute of Technology in Lausanne, Switzerland, has revealed a new accessory that may make the contact lenses more appealing for the average person by making them more reactive. When a user covers one of the reflectors by winking, the glasses change their polarization. Two kinds of polarized light take two different paths through the contact lenses, activating the normal or magnified view. The research team, which includes the University of California, San Diego as well as experts at Paragon Vision Sciences, Innovega, Pacific Sciences and Engineering,

Reminiscent, the team say, of Luke Skywalker’s artificial hand in Star Wars, the electrodes in the bionic limb would wrap around the nerve endings in the arm. This would mean that for the first time the hand could communicate directly with the brain, sending back information about temperature and pressure. Funded by the Engineering and Physical Sciences Research Council, and led by Dr Kianoush Nazarpour, a lecturer in Biomedical Engineering at Newcastle University, the team hope to develop technologies to give amputees a limb that more closely mirrors the real thing. Dr Nazarpour, who is part of Newcastle University’s Biomedical Engineering team, said: “The UK leads the way in the design of prosthetic limbs but until now one of the limiting factors has been the technology to allow the hand to communicate with the brain.

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“If we can design a system that allows this two-way communication it would help people to naturally reach out and pick up a glass, for example, whilst maintaining eye contact in a conversation, or pick up an apple without bruising it. “This will advance the field of prosthetics, provide enhanced function to prosthesis users, and also reduce the time involved to learn how to use the device because the movements will come naturally. “The technology will also have applications for patients with neurological conditions where reduced sensation is a factor.” Steve Austin it might not be but technology is well on the way towards breakthroughs that were just the stuff of fiction in 1970s.


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FEATURE z

The UK leads the way in the design of prosthetic limbs but until now one of the limiting factors has been the technology to allow the hand to communicate with the brain. Dr Kianoush Nazarpour

Biomedical Engineering team, Newcastle University

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BIOSCIENCE JOURNAL SPRING 2015

ADVERTORIAL

Accreditation: Delivering Confidence in Health Services The quality of health and social care services is under constant and close scrutiny. Professor Sir Mike Richards, Chief Inspector of Hospitals at the Care Quality Commission (CQC) has recently acknowledged that accreditation and peer review processes already play an important part in stimulating and supporting quality improvements.

The role of UKAS accreditation within the health and social care sector has also recently been formally recognised in a joint policy agreement released by the Department of Health (DH) and Department for Business, Innovation and Skills (BIS). The DH/BIS policy agreement highlights that “Accreditation increases trust in conformity assessment and thus reinforces the mutual recognition of products, processes, services, systems, persons and bodies across the EU”. It goes on to state that where new quality assurance schemes are planned in the NHS or social care, particularly where there is interest in schemes awarding certification or accreditation, their initiators should work with The United Kingdom Accreditation Service (UKAS) from an early stage to ensure that the schemes are sufficiently rigorous to meet EU and UK accreditation requirements. The drive for accreditation in the health sector is mirrored in the NHSE business plan for 201415 to 2016-17. A key deliverable of the plan is to “ensure more than 70% of all scientific and diagnostic services are part of accreditation programmes and demonstrate robust quality assurance measures by end of March 2015.” Whilst this may appear to be an ambitious target, as the UK’s National Accreditation Body, UKAS already underpins quality in the delivery of a number of health and social care services. These include pathology, diagnostic imaging (ISAS), point of care testing and physiological services (IQIPS). A pilot scheme for the accreditation of inspections of residential adult social care providers began in July, with the first accreditations due in December 2015.

Sponsored by Professor Sue Hill, Chief Scientific Officer for England at DH, the IQIPS programme was created by the Royal College of Physicians (RCP) with the aim of improving the quality of services, care and safety for patients undergoing physiological science service tests, examinations and procedures. It covers a range of eight physiological diagnostic specialisms including audiology, cardiac physiology, gastrointestinal physiology, neurophysiology, ophthalmic and vision science, respiratory and sleep physiology, urodynamics and vascular science.

ultrasound services. Richard Pole, Operations Director at IVS said: “Achieving this badge of quality is something we are particularly proud of, as it represents independent external recognition and affirmation of our good practices, giving confidence to both patients and health care professionals alike. We have found that becoming accredited has driven up the quality of our services and supports the sharing of good practice. It will also hopefully enhance the awareness of vascular ultrasound as a profession across the UK, and could be used as leverage for change.”

Highlighting the benefits of the scheme, Professor Hill said. “IQIPS puts physiological scientific services at the leading edge of continuous quality improvement and quality assurance in the NHS. It provides a mark of quality for commissioners, providers and users of service with patient quality outcomes at its core.”

For further information on the IQIPS programme please visit http://ukas.com/ Library/Media-Centre/PromotionalMaterials/Brochures/IQIPS Brochure.pdf

Independent assessment and accreditation is a key part of the IQIPS programme and UKAS has been contracted by RCP to deliver the national assessment and accreditation service for all eight physiological diagnostic specialisms. The first IQIPS accreditation was granted to Action for Deafness for adult hearing services at the beginning of 2013. Since then a further 15 audiology services providers from across the public and private sector have achieved IQIPS accreditation. UKAS is working closely with the RCP on a plan for the staged roll out of accreditation to each specialism. This year Independent Vascular Services (IVS) Ltd became the UK’s first vascular laboratory to gain ISAS accreditation for its range of vascular

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BIOSCIENCE JOURNAL SPRING 2015

z FEATURE

fantastic voyage In 1966, movie-goers were treated to the release of a film called Fantastic Voyage, a Cold War science fiction thriller about a scientist who is nearly killed in an assassination attempt. As he hovers between life and death, a medical team is reduced to microscopic size then ventures into his body to carry out the delicate brain surgery needed to save his life. Starring Stephen Boyd, Raquel Welch and Donald Pleasence, it was an entertaining romp and all based on fantasy. Little people journeying through the human body? All very Hollywood but it could never really happen, yes? Well, yes. And no. We may not be able to shrink people, probably never will, but the concept that ‘small is beautiful’ is interesting medical science more and more. Researchers can increasingly see the benefit of the emerging science of nanotechnology as a way of carrying out previously invasive procedures and also adding immeasurably to their knowledge of the human body. Nanotechnology is the industry in which tiny computers called nanites work throughout whatever object into which they are inserted, operating at the molecular level.

The concepts behind modern nanotechnology were first given international exposure by physicist Richard Feynman in 1959, who gave a speech in which he talked about how we would one day be able to manipulate atoms and molecules and craft them into whatever we wanted them to be. He went on to discuss the possibility of creating extremely small machines that would serve as tiny tools. Since then, the idea has taken shape and nanotechnology - the science of the small is coming of age and is capable, say medical scientists, of being used extensively for everything from replicating cells to analysing broken bones. There are already some exciting examples of its application. Take the work being done at Harvard University in the United States where scientists have designed the first large DNA crystals with precisely prescribed depths and complex 3D features, which they say could create revolutionary nanotechnology devices. DNA has potential as a platform that could support new nanodevices in computer science, microscopy, biology and researchers have been working for twenty years to coax DNA molecules to self-assemble into the precise shapes and sizes needed in order to make the nanotechnology work. Key to that that has been designing large DNA crystals with precisely prescribed depth and complex features, something now achieved by a team at Harvard’s Wyss Institute for Biologically Inspired Engineering. The team built 32 DNA such crystals using a ‘DNA–brick self–assembly‘ method, rather similar in concept to Lego, which was first

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demonstrated in 2012 when they created more than 100 3D complex nanostructures about the size of viruses. The new crystal structures are more than 1,000 times larger than those early structures, closer to a speck of dust in size, which qualifies as large in the world of DNA nanotechnology. William Shih, Ph.D., who is co–author of the study and a Wyss Institute Founding Core Faculty member, as well as Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the DanaFarber Cancer Institute, is excited by the potential. He said: “My preconceived notions of the limitations of DNA have been consistently shattered by our new advances in DNA nanotechnology. DNA nanotechnology now makes it possible for us to assemble, in a programmable way, prescribed structures rivalling the complexity of many molecular machines we see in Nature.”


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FEATURE z

My preconceived notions of the limitations of DNA have been consistently shattered by our new advances in DNA nanotechnology. William Shih, Ph.D.

Associate Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

CONTINUED ON PAGE 42

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NANOTECHNOLOGY’S ROLE IN DELIVERING DRUG TREATMENTS

The development of DNA technologies is just one possible application for nanotechnology. Scientists are also realising its potential for the delivery of drugs. In America, LayerBio, which develops drug delivery products for ophthalmology and wound care applications, has received a $150,000 research grant to support development of its nanoparticle-based glaucoma therapy, from the National Science Foundation.

Figure 1: Developed by Wyss Institute Core Faculty member Peng Yin and his team, the DNA-brick selfassembly method uses short, synthetic strands of DNA that bind and interlock like Lego® bricks. Credit: Wyss Institute at Harvard University.

Glaucoma is the leading cause of irreversible blindness worldwide. In the United States alone, an estimated 2.2 million people suffer from it and the typical first-line treatment for glaucoma is eye drops. However, in many cases, lack of continuous release of the drug and issues with patients using the droppers properly reduces the effectiveness of the treatment. LayerBio is developing a biodegradable nanoparticle drug delivery system for an improved release of the drug over a minimum of four to six months per dose. The advantages of the company’s LayerForm technology include its ability to incorporate small molecules. Dr Ken Mandell, LayerBio’s Founder and CEO, said: “It is critical that we develop long-acting alternatives to eye drops that provide aroundthe-clock coverage for patients suffering for glaucoma. The ability to offer continuous coverage and guaranteed compliance is vital to preventing progression of disease.”

DNA brick crystals: Researchers have achieved 32 different-shaped crystal structures using the DNAbrick self-assembly method. Credit: Wyss Institute at Harvard University Nanotechnology has helped the team‘s work take great strides forward and the same is true of cancer treatments. Also in the US, scientists are working on ‘nano-cocoons’, an idea being developed by a team at North Carolina State University and the University of North Carolina, where the co-authors on the research project include PhD students Yue Lu, Margaret Reiff and Tianyue Jiang and Dr Ran Mo, a former postdoctoral biomedical engineering researcher. Each bio-engineered cocoon consists of a single DNA strand in the shape of a ball of yarn, which is 150 nanometers wide and which can carry large amounts of anti-cancer drugs to release into cancer cells.

carries folic acid molecules known as ligands that bind to cancer cells and force them to suck in the nano-cocoon. Also, the nanococoons are less toxic than other systems which use synthetic materials and are easier to manufacture because of their self-assembly nature. Dr Zhen Gu, senior author of a paper on the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill, said: “We’re very excited about this system and think it holds promise for delivering a variety of drugs targeting cancer and other diseases.”

The team says that the surface of the cocoon

Figure 2: A key advantage of the DNA brick method is its modularity, which allows for a variety of prescribed crystal shapes to be designed and constructed. Credit: Wyss Institute at Harvard University CONTINUED ON PAGE 45

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ADVERTORIAL

Nanomedicine - bridging the skills gap Nanomedicine is at the forefront of modern healthcare. Nanoparticles offer a new platform for drug delivery that can extend the “patent life” of drugs, but also greatly increase the targeting and effectiveness of therapy.

In addition to drug delivery, nanoparticles can also enhance most of the medical imaging modalities, and in some cases offer combined diagnostics and therapy - now called “Theranostics”. Nanotechnology is providing the basis for many of the new regenerative medicine approaches that are based on artificial scaffold structures and it offers solutions for many of the new generation of point-of-care biosensors and some of the advanced gene sequencing instrumentation. There are already early indications of improved healthcare outcomes, and the creation of new business and industry. However, training in this area is currently falling behind the expansion of knowledge, and there is a developing need to train practitioners in new areas of medical care, business and industry, as well as provide Continuing Professional Development (CPD) for professionals working in this field, giving

them access to new opportunities and developments. Without this multidisciplinary approach, the necessary knowledge transfer across the sectors will not occur, and we will not see the patient and healthcare benefits that should technically be possible.

Dr Christiane Norenberg

The University of Oxford offers an extensive postgraduate CPD programme in nanotechnology and nanomedicine (http:// www.conted.ox.ac.uk/nano), drawing on Oxford’s well-established and universally recognized reputation for nanotechnology research and teaching. These flexible, part-time programmes, summer schools and short courses are designed for professionals working across disciplines and industries, and provide insights into the very latest advances in knowledge, skills and techniques in nanotechnology and nanomedicine.

Dr Christiane Norenberg is Nanotechnology Business Manager at the University of Oxford’s Begbroke Science Park and Course Director of Oxford’s CPD Programme in Nanotechnology and Nanomedicine, delivered by the Department for Continuing Education.

Begbroke Science Park Department for Continuing Education

Nanotechnology Programme Nanomedicine Summer School 29 June – 3 July 2015 Delivered by internationally recognised experts. Attend the full week or selected days. 29 June: Introduction to Nanomedicine; Challenges 1 July: Nanomedicine – Diagnostics and Opportunities 2 July: Nano-Biosensors 30 June: Nanotechnologies for Regenerative 3 July: Nano-Pharmaceuticals Medicine and Tissue Engineering

Part-time online Postgraduate Certificate in Nanotechnology Comprises: • The Wider Context of Nanotechnology • The Fundamental Science of Nanotechnology • Fundamental Characterisation for Nanotechnology • Nano-scale Materials Characterisation (residential weekend) All modules and the residential weekend can also be taken independently as short courses. For further details and application forms, visit www.conted.ox.ac.uk/nano or email nano@conted.ox.ac.uk, tel +44 (0)1865 286955

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BIOSCIENCE JOURNAL SPRING 2015

ADVERTORIAL

Striking a note of caution as the use of nanotechnology in medicine gathers pace Nanotechnology may be advancing at a rapid rate but these are still early days and much still needs to be done as the medical world tries to keep pace with the dramtic pace of development. That is the message from Dr Gavin Jell, Lecturer in Nanotechnology & Regenerative Medicine at University College London, who runs an MSc course on the technology’s applications in medicine.

Dr Jell, who works at the UCL Centre for Nanotechnology & Regenerative Medicine in the Division of Surgery and Interventional Science, believes that the excitement about the potential of nanotechnology needs to be combined with robust cross-disciplinary evaluation of safety. He said: “There are some fantastic technologies being developed in nanotechnology, particularly in the field of targeted drug delivery, diagnosis and even theranostics, but we should remember that this is still a fledgling technology. “There is often a balance between the complexity of the drug delivery system and translational reality. The simpler the technology the higher the commercial

MSc Nanotechnology and Regenerative Medicine UCL is a world-leading centre of excellence for nanotechnology, stem cell research and regenerative medicine. Our cutting-edge research feeds directly into this innovative taught graduate programme hosted by an institution that is most cited by health professionals*.

// Discover cutting-edge technologies that are transforming modern medicine. // Learn about translational research with world renowned academics and surgeons. // Develop exceptional practical skills during a six-month lab-based project. *Thomson Scientific Citation Index

www.ucl.ac.uk/nanomed

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potential. The more complicated the technology (e.g. multi-modality particles for imaging, diagnosis and treatment) the greater the translation cost and the regulatory challenges. “We think its important to expose our students (taught and research) to the commercial and clinical realities of the use of nanotechnology in medicine by having a close relationship with both clinicians and the emerging businesses exploiting these technologies. This will hopefully allow the development of clinically and commercially relevant research - that will deliver real improvements to patient care.


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But what of the future? So nanotechnology is already producing developments but what is its potential? Well, the opportunities are huge and the work already under way could just be the start.

For example, the science could greatly speed up the process of creating vaccines because you could theoretically load many nanites with different vaccines and inject them into the host all at once to see if any of them work.

Nanotechnology may also play a role in cancer treatment. For example, odits are gold nanites that are able to track down cancer cells in the body and nanoparticles may be able to inject chemotherapy directly into cancer cells with minimal damage to the surrounding cells. And biomarkers will able to attach themselves to diseased cells so that a doctor can analyse them. Some of this is happening now, other developments may take longer to come to fruition - and we may never create another tiny Raquel Welch - but one thing seems certain. Some may argue that the future is small but the potential is huge.

Some scientists say that nanites will one day be able to run throughout our bodies via the circulatory system, through our blood, to monitor vital signs such as broken bones, torn muscle tissue, irregularities in metabolism levels and cholesterol levels.

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Some scientists say that nanites will one day be able to run throughout our bodies via the circulatory system, through our blood, to monitor vital signs such as broken bones, torn muscle tissue, irregularities in metabolism levels and cholesterol levels.


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Out of this w

At first glance, one of the most stunning achievements in space exploration, an investigation into rickets in sailors who died 470 years ago and cutting-edge cancer research may appear to have little in common. However, all three have shown the immense potential offered by mass spectrometry and spectroscopy tools which are giving bioscience researchers fascinating information about the world in which we live. And about other worlds, too, because in November 2014, the potential of the technology was brought to global attention when, after a ten year journey in which it travelled more than 6.4 billion kilometres, the European Space Agency’s Rosetta spacecraft delivered a lander onto a comet, a first for science. To much cheering in mission control, the Philae lander touched down on 67P/ Churyumov-Gerasimenko and was able to send back vast amounts of data before its position under a rocky outcrop meant that its solar energy faded and it went into hibernation. One of nine experimental systems on board Philae was a miniaturised mass spectroscopy system which measured

isotope ratios in material sampled from the comet’s surface and atmosphere. Constructed with help from Raymond E. March, Professor Emeritus in the Department of Chemistry at Trent University in Peterborough, Ontario, Canada, and John F.J. Todd, Emeritus Professor of Mass Spectroscopy at the University of Kent in the United Kingdom, the use of the system showed how flexible the technology can be for bioscientists. Spectroscopy is the study of light as it breaks into its constituent colours. By examining the colours, researchers can determine the properties of the object being studied because they reflect energy states. The field is divided into many subdisciplines, depending on what is being measured, including mass spectrometry which is used for measuring the molecular mass of a sample and has applications in biotechnology, pharmaceuticals and the environmental field where it can examine water quality and food contamination.

Comet 67P/Churyumov-Gerasimenko

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world

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What is a mass spectrometer?

A historical case with modern significance In the medical field, spectroscopy technology is being used for research into 470-year-old bones which may have relevance to modernday sufferers of the bone condition rickets.

At first glance, the research into a condition in drowned sailors 470 years ago may seem to have little relevance to modern day but, in fact, it may be more useful than it at first appears.

The technology helped scientists confirm that many sailors who died on Henry VIII’s warship Mary Rose had rickets in childhood. The vessel, the king’s flagship, sank in the Solent, off Hampshire, in 1545, resulting in the deaths of more than 400 men.

According to the research team, the Raman technique may have a place in modernday detection of the condition, which is of particular interest because of concerns that conditions such as rickets are making a comeback in some countries due to the effects of poverty.

Some of the sailors’ bones were analysed using Raman spectroscopy, a pioneering nondestructive laser technology, in an attempt to identify evidence of bone disease. Two sets of tibias were obtained from The Mary Rose Trust, some that appeared anatomically healthy and some that were abnormal in shape. The deformations in the abnormal bones were suspected to be due to a metabolic bone disease such as rickets, which is caused by poor diet. The Raman study confirmed that the abnormally shaped bones did indeed have chemical abnormalities. The RAMAN study, led by Professor Allen Goodship, was funded as part of a £1.7 million grant from the Engineering and Physical Sciences Research Council and the bones were measured in a laser facility at the Institute of Orthopaedics UCL. The ‘normal’ bones that were analysed as part of the study were supplied by the Vesalius Centre at the University of Bristol.

Dr Jemma Kerns, RAMAN Clinical Study Manager at UCL and RNOH, one of the scientists who conducted the study, said: “This is the first time that this laser technology has been used to study bone disease in archaeological human bone. “We have identified chemical changes in the bones, without damaging them. There is strong evidence to suggest that many of the sailors had suffered from childhood rickets and we hope to apply the Raman technique to the study of modern day rickets.” Alex Hildred, Curator of Human Remains at the Mary Rose Trust, said: “The Mary Rose Trust has the responsibility for the remains of over 179 individuals who perished with the ship. “Their provenance is absolute; they represent the crew of an English warship in July 1545. The human remains have potential to make a contribution to the public through research, education, display and interpretation.”

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A mass spectrometer is a an analytical instrument that measures the mass-tocharge ratio (m/z) of charged analytes (ions). Often the mass spectrometer, or downstream software, can determine the charge as well. Thus, the instrument can effectively provide mass measurements rather than m/z measurements. For example, if the instrument detects an ion of m/z 500 Daltons but it can be determined that the charge is 2+, then the mass (m) is 1000 Daltons. An important feature is that a modern mass spectrometers can measure many analytes simultaneously. Thus, complex mixtures of analytes can be introduced to the mass spectrometer at once. The mass spectrometer will analyze the mixture and output a mass spectrum showing a peak at each m/z that was detected. Scan times differ between instruments but the typical times to get a full mass spectrum range from 100 milliseconds up to a second. The range of masses that can be measured, the accuracy or the measurements, and the resolution that can be achieved vary greatly depending on the instrument. See the mass analyzer section for more details. The height of each peak is representative of how many ions are being detected at that particular m/z. These peaks are not directly quantitative; however, careful use of internal standards and references can provide quantitative information.

WHAT ARE MS1 AND MS2?

MS1 and MS2 refer to two very broad categories of MS scan types. One of the primary uses of mass spectrometry is to identify peptides and proteins. It is often not possible to do this by m/z measurement alone so commonly mass spectrometry methods involve fragmentation of petides and measurement of the of the resulting m/z ratios. Scans which measure m/z ratios without fragmentation are termed MS1 scans. Scans involving fragmentation are MS2 scans.


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Technology offers insights into cancer Mass spectrometry is helping medical research in many other ways as well, including exciting work being done in the United States. Scientists at the Shimadzu Institute for Research Technologies and the Department of Chemistry and Biochemistry at The University of Texas (UT), at Arlington, have used the technology to develop a new method for detecting trace amounts of estrogen in small samples. The hormone estrogen has been linked to everything from tumour growth to neuron loss during Alzheimer’s disease but detecting very small amounts in blood and other biological fluids can be difficult. To address that, a UT Arlington research team used advanced mass spectrometry and chromatography instrumentation at the Shimadzu Institute to develop a method for detecting trace amounts at less than 10 parts per trillion in a 100 microliter sample, equivalent of a drop of water in 20 Olympicsize swimming pools.

Mass spectrometry and chromatography were used to separate, identify, and quantify molecules in a complex mixture. Kevin Schug, Shimadzu Distinguished Professor of Analytical Chemistry at UT Arlington, said: “We are dealing with extremely small quantities and there are a lot of things out there that look like estrogen. You have to have this ability to separate these individual components and detect them accurately.” Jana Beinhauer, a visiting scientist from Palack University in the Czech Republic who spent nine months working at UT Arlington, and lead author on the paper outlining the findings, said: “Estrogens perform important biological functions not only in sexual development and reproduction but also in modulating many other processes impacting health and diseases in human and animals,. “The metabolically active estrogens exert strong biological activities at very low circulating concentrations. Therefore, this research is very important for finding sensitive, efficient, fast, automated and simple method how to determine the trace estrogens in serum.”

Jose Barrera, Director of the Shimadzu Institute and a co-author on a new paper outlining the findings, said: “This new method pushes the detection limit for estrogens to a level that is applicable to research, human health, medicine, and environmental analysis.” The technology promises, it would seem, to keep pushing the barriers even further.

This new method pushes the detection limit for estrogens to a level that is applicable to research, human health, medicine, and environmental analysis Jose Barrera

Director of the Shimadzu Institute

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BIOSCIENCE JOURNAL SPRING 2015

z FEATURE

Aiming high encouraging young people into the world of science Talk to anyone in the bioscience world and they will tell you that one of their major concerns is the dearth of young people coming out of schools, colleges and universities having studied science and technology. Where, they ask in a world of Humanities, are we going to find the next generation of young researchers, the young people whose passion for science has been fired up and who will go on to university to make the staggering discoveries on which the industry relies? Well, governments and educational institutions have been thinking the same thing and in the UK a campaign has been launched to show young people the career opportunities that can be unlocked by studying science and maths. Backed by industry, the Your Life campaign aims to raise young people’s participation in science maths and physics A levels by 50 per cent in three years, seen as vital because the UK faces an annual shortfall of 40,000 workers with scientific and mathematical skills.

Edwina Dunn, Chair of Your Life, said: “Most young people in the UK aspire to a career in business, but very few are being shown the right way to get there. In a changing world dominated by technology, it is the skills learned from studying mathematics and science that will matter most. Yet these are exactly the subjects that the vast majority of 16 year olds are turning away from – put off by the misconception that maths and science aren’t relevant to their future. “The Your Life campaign has been created to change that image - to show that the mathematics and science students of today will be the CEOs of tomorrow.” Such approaches seem to be working because more students are taking A levels in STEM subjects, according to results published by the UK-based Joint Council for Qualifications. Since June 2010, entries in subjects like maths and the sciences have risen across the board with: • biology up 10.7% • chemistry up 21.5% • physics up 18.5% • maths up 15.3% • further maths up 20.1% The results also showed that since 2010 more women are taking exams in science, technology, engineering and maths subjects with A level entries rising in:

The campaign is being led by a group of leading companies including BAE Systems, Carillion, Ford, Johnson & Johnson, Nestle, Rio Tinto, Shell and Visa and supporters include Maths whizz Rachel Riley, Presenter of Channel 4’s quiz show Countdown and Polar explorer Ben Saunders.

• maths: up by 10% • physics: up by 16% • chemistry: up by 23% • biology: up by 16% Nevertheless, there is still a long way to go and widespread concern about the

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skills shortage was highlighted recently by a report from the Instructus Group, the UK’s largest provider, registration and certification authority for apprenticeships and worked based education. Instructus, which has worked with such names as BT, BAE Systems, GlaxoSmithKline, McAlpine, Santander and Nestle, said that although the economic upturn was welcome, the skills shortage remained a profound worry. The report says that over the next three to five years, UK businesses expect to increase the number of jobs requiring leadership and management (73%) and higher skills (71%). However, 23% of employers stated in a recent CBI survey that they are not confident of filling their more highly skilled roles. Instructus says that with increases in the cost of university education, apprenticeships are increasingly viewed as a genuine alternative with the potential to reach degree and even masters levels. The company says that the old image of apprenticeships being solely for


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BIOSCIENCE JOURNAL SPRING 2015

z FEATURE

SCHOOL SEEKS TO INSPIRE THE SCIENTISTS OF TOMORROW One place where the message about inspiring young scientist has found a welcome is Liverpool where the first school in the UK to specialise in Science and Healthcare was recently awarded STEM Assured® status.

The award for Liverpool Life Sciences UTC, which is in Liverpool’s Baltic Triangle, recognises outstanding work across STEM subjects.

the young is no longer true; Instructus provide vocational work place education and employment to people of all ages and across all industry sectors and occupational groups. The Instructus report suggested some key points for bridging the UK skills gap: * There needs to be a recognition that people don’t stay in jobs for life. All work based education must fulfil the immediate need, but be entirely transferable to other sectors

* Training must become increasingly outcome oriented - this means development of individuals must focus on what they can do (dynamic skills) rather than what they know (cognitive skills) * Training providers must focus more on employers’ needs and positive outcomes. They must also deliver additional benefits to their customers, including recruitment of appropriate individuals to bridge skills gaps, and consultancy services. David Holland, CEO of Instructus, said: “We invite employers to enter into a dynamic consultancy process, the outcome of which is often a long-term strategic partnership. “Not everyone can afford the time or cost of university and frankly, there’s little substitute for learning in a hands-on manner from people skilled and experienced in the field, no matter what your age. “This training will go a long way to not only filling the skills gap, but ensure those employers educating their workforces now are

essentially future-proofing not only their own business, but to a large extent, the continued growth and development of the nation.”

Most young people in the UK aspire to a career in business, but very few are being shown the right way to get there. In a changing world dominated by technology, it is the skills learned from studying mathematics and science that will matter most. Yet these are exactly the subjects that the vast majority of 16 year olds are turning away from – put off by the misconception that maths and science aren’t relevant to their future.

Edwina Dunn Chair of Your Life

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As the first school in the UK to specialise in Science and Health Care for 14 to 19 year olds, Liverpool Life Sciences UTC is now also one of only 20 colleges in the country to receive the award. Liverpool Life Sciences University Technical College gives 14-19 year olds the opportunity to take a full time programme of study specialising in either Science or Health. It brings together the University of Liverpool, The Royal Liverpool and Broadgreen University Hospital Trust and major local employers like Novartis, Redx Pharma, Actavis and Pro-Lab Diagnostics, offering students the skills and work-related learning experience to improve their employability within the Science and Healthcare sectors. For Lyndsay Macaulay, director of enterprise at Liverpool Life Sciences UTC, the school’s determination to encourage young people to view science as a valid career option can only benefit the country. Lyndsay said: “By providing our young people with a gateway to globally recognised businesses through the STEM network, we can support and inspire them as they embark on the challenges of tomorrow.”


BIOSCIENCE JOURNAL SPRING 2015

ADVERTORIAL

Education secretary backs the drive to recruit more young scientists UK Education Secretary Nicky Morgan is backing attempts to enthuse young people with a love of science.

“Nor are they subjects that you can only succeed in if you went to the right school or had the right connections. In fact, quite the opposite - success in the sciences is one of the biggest drivers of social mobility, enabling young people from a range of backgrounds to access highly paid careers and opportunities. That’s why it’s so important that the study of these subjects isn’t just limited to a handful of schools who coach their students - it isn’t just unfair, it’s a waste of talent as well.

She said: “Developing the best schools and skills is a key part of our long-term economic plan to secure Britain’s future, and the skills taught by subjects like maths and science are some of those most valued by employers and universities. That’s why I am pleased to support the Your Life campaign to encourage more young people, and especially girls, to study these subjects by showing the exciting opportunities they can bring. “Our plan for education will ensure that all young people leave school with the knowledge and skills they need to succeed in life in modern Britain. Increasing the focus on STEM subjects is a key part of this as it will empower girls and boys equally to leave school able to get a job and get on in life. “The truth is, our world is changing beyond recognition, at a pace unmatched by any other point in history. That change is affecting our country in all sorts of positive ways, but it also means that, to succeed in the global economy, the British workforce of tomorrow has to have the skills and knowledge to compete in that changing world. “Even a decade ago, young people were told that maths and the sciences were simply the subjects you took if you wanted to go into a mathematical or scientific career, if you wanted to be a doctor, or a pharmacist, or an engineer. “But if you wanted to do something different, or even if you didn’t know what you wanted to do, and let’s be honest - it takes a pretty confident 16-year-old to have their whole life mapped out ahead of them - then the arts and humanities were what you chose. Because they were useful for all kinds of jobs. “Of course now we know that couldn’t be further from the truth, that the subjects that keep young people’s options open and unlock doors to all sorts of careers are the STEM subjects: science, technology, engineering and maths. “The skills gained from studying these subjects come in useful in almost any job you could care to name - from the creative and beauty industries to architecture. Even in my former profession: the legal sector is crying out for more science graduates as patent law becomes big business.

“And you don’t have to be male to be taken seriously in the STEM industries. I care deeply about the futures of today’s young women, about their academic choices, about their career successes. “If we want to make the most of half of our workforce, if we want to eliminate the gender pay gap and if we want that same half of the workforce to succeed in jobs that boost our economy, then we must make sure that teenage girls don’t feel, and certainly aren’t told, that certain subjects are the preserve of men. “

“That’s why it’s so important that young people are aware of the opportunities these subjects bring, because they’re not nearly as popular as they should be In 2011, only 19% of girls who achieved an A* in GCSE physics went on to study it at A level. And whilst the figure for boys is better, it’s still under half. “There’s the same issue with maths. Fewer than two thirds of girls who achieved an A* in maths GCSE went on to study it at A level. And yet maths, as we all know, is the subject that employers value most, helping young people develop skills which are vital to almost any career. And you don’t just have to take my word for it - studies show that pupils who study maths to A level will earn 10% more over their lifetime. “These figures show us that too many young people are making choices aged 15, which will hold them back for the rest of their life. “By working with these young people, this campaign is going to help dispel the myths about STEM subjects because they’re not stuffy, boring subjects for people who don’t get outdoors much. Far from it - they’re the keys to the most cutting edge, fast-paced areas of work and they’re behind some of the most exciting new developments in this country and around the world.

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Of course now we know that couldn’t be further from the truth, that the subjects that keep young people’s options open and unlock doors to all sorts of careers are the STEM subjects: science, technology, engineering and maths. Nicky Morgan

UK Education Secretary


BIOSCIENCE JOURNAL SPRING 2015

ADVERTORIAL

Developing long term relationships with the skilled workers of the future Despite the great demand for skilled workers in the STEM industries, employers are struggling to find and retain the young people with the skills and knowledge necessary to succeed in the workplace. A recent survey from PWC found that 84% of British bosses are concerned about the finding young people with the right skills. Employers look for industry specific skills when hiring graduates. It is therefore important to invest in the next generation of workers and give undergraduates the opportunity to develop these vital employability skills.

Summer placements are extremely beneficial for students and employers alike. Hosting a placement enables an employer to create links with universities which can offer longer-term possibilities including research opportunities and strong brand recognition amongst students. An employer can benefit from accessing a talented, enthusiastic member of staff who can help with project work and fill capacity during the summer. Not to mention that investing in industrial placements will provide the scientists of the future with the practical skills necessary to succeed in graduate positions. Employers have, however, reported limitations with the traditional summer placement model, including not being able to establish a strong relationship

during the placement and after inductions, the student not having long enough to produce meaningful work.

In response to this, the Industry Degree Scheme (IDS) has been developed by industry bodies and employers representing the Science Industry Partnership (SIP). Employers within the SIP recognise the importance of developing the next generation of scientists through offering industrial placements. The Scheme builds upon the traditional summer placement model by offering a minimum of two summer placements which enables employer and students to build a long term relationship. The IDS incorporates existing degree programmes from a network of universities with a minimum of two summer placements which are undertaken in the ‘sponsor’ company. Students are linked with the sponsor company for the duration of the scheme and graduate with an enhanced degree potentially leading to a full time position in the sponsor company. Through the IDS, students will develop sector specific and company abilities and then be equipped to enter a professional role upon completion of their degree. Employers are able to develop a longitudinal relationship with potential employees whilst they are undertaking their academic

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programme, minimising the risks of recruitment and retention of graduates within the sector. Employers will engage with students in their first year of study and help them to develop and learn in line with company policy and requirements. The student will acquire the skills and training in the first placement to jump straight into meaningful work in their second placement. At the end of the placement, the student will have company specific knowledge ideally leading to a full time position. Cogent, the expert delivery partner of the SIP plays a pivotal role in matching employer needs with students who are developing the knowledge base and wider qualities sought by the company. The Industry Degree Scheme will provide more opportunities for students to gain the hands on experience they are currently lacking, helping to reduce the skills gap. Employers taking part will contribute to the development of a future talent pool with the capabilities that the science sector needs for years to come. For more information about the Science Industry Partnership or Industry Degree Scheme please email info@cogent-ssc.com


BIOSCIENCE JOURNAL SPRING 2015



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