This year’s Cambridge Festival of Ideas will host over 200 events, exhibitions and performances as it explores the theme of extremes, from political and social radicalism to life at high altitudes and the extreme high street.

The Festival, now in its 11th year, runs from 15th to 28th October. Speakers include Baroness Valerie Amos, musician Evelyn Glennie, Rowan Williams, Professor David Runciman, best-selling author Tara Westover, film director Tim Slade, author James Bloodworth, psychologist Terri Apter, Professor David Reynolds, economist Victoria Bateman, postcolonial literature expert Priyamvada Gopal and international trade economist Meredith Crowley.

The programme launches online today and is packed with events ranging from debates, talks, exhibitions, films and performances held in lecture theatres, museums and galleries around Cambridge. There are events for all ages and most are free.

Debates include:

- Wars in the Middle East: living through extremes. What happens to those who choose not to flee during war situations in the Middle East? With BBC journalist Nawal El Maghafi, anthropologist Dr Lori Allen, Sophie Roborgh and Mona Jebril. [16th October]

- Europe in an age of extremes. With huge internal and external pressures facing the European Union, including the rise of nationalist and populist movements of all types across Europe - both inside the EU and outside, as well as the power struggle going on for control of Europe, can it survive? With Ian Kearns, Dr Julie Smith, Professor John Breuilly and Timothy Less. [18th October]

- The future of work. Will the future of work be one in which jobs become ever more precarious and robots take over or can we regulate to make the gig economy and artificial intelligence work in our favour? With author James Bloodworth, Dr Alex Wood, Dr Hatice Gunes and Ben Dellot from the Royal Society for the Arts. [20th October]

- What does a global Britain mean post-Brexit? Has Brexit highlighted a need for a broader discussion about immigration and Britain's place in the world today? With historian Shruti Kapila, Richard Johnson from Lancaster University, Sundeep Lidher and Professor Philip Murphy. [23rd October]

- Bridging the gender gap. What does gender equality mean in practice? Is feminism a threat to men or a collective liberation from social stereotypes? Can there be equality at work without equality at home? With Dr Victoria Bateman, Dr Manali Desai, film, tv and theatre director Topher Campbell and Duncan Fisher from the Family Initiative. [24th October]

- Trade wars: deal or no deal?: What is the likely impact of trade war and how has the tension between protectionism and free trade played out in history?  A panel discussion with Dr Marc-William Palen, Dr Meredith Crowley, Dr Lorand Bartels and economist Rebecca Harding. [20th October]

Other sessions include:

- Praise and blame. Psychologist Dr Terri Apter  on how being judgmental shapes our relationships and why it may not be such a bad thing. [22nd October]

- Educated: a journey towards independence. Author Tara Westover in conversation with Guardian columnist Hadley Freeman about her best-selling memoir, Educated. [20th October]

- Anticolonialism and the making of British dissent. Dr Priyamvada Gopal on the ways in which colonial subjects took up British ideas and turned them against empire when making claims to freedom and self-determination. [25th October]

There will also be a range of hands-on sessions for adults such as a range of events in the Law Faculty covering everything from ethical dilemmas in medical imaging and what we can do with plastic wastes as well as many events for children, including an interactive Arctic Day, Mini Movers in the Museum, a making giants workshop, a pre-history day and interactive languages events on everything from translation to dying languages.

The Festival is a multi-media cultural event. There will be cinema screenings of films such as Tim Slade’s The Destruction of Memory on cultural destruction over the past century; exhibitions on subjects ranging from the NHS, refugees on Europe’s borders, the extreme high street and the first women computer programmers; and a range of events and performances at the Cambridge Junction.

The Festival will also see the launch of Centre for the Study of Global Human Movement with events including a discussion on rethinking humanitarianism with Rowan Williams, the former Archbishop of Canterbury.

Ariel Retik, manager of the Cambridge Festival of Ideas, said: "The Festival of Ideas aims to challenge people’s received ideas and to question the status quo. The theme of this year's Festival is extremes. We’re living in an age where everything seems to be growing more extreme – whether politics, income inequality, the climate or technology – and we want to explore this in its broadest sense.

"A core aim of the Festival is to share with the public some of the incredible research and thinking that is happening in Cambridge and beyond across disciplines and institutions and to encourage an exchange of ideas between audience and researchers. Every year, we welcome thousands of people to hundreds of events, including talks, debates, performances, films and exhibitions. This year, we look forward to doing the same.”

The Festival sponsors and partners are St John’s College, Anglia Ruskin University, RAND Europe, University of Cambridge Museums and Botanic Garden, Cambridge Junction and Cambridge University Press. The Festival media partners are BBC Radio Cambridgeshire and Cambridge Independent.

*Bookings for the Festival of Ideas open in September.

Find out more on Facebook:  http://www.facebook.com/cambridgefestivalofideas and on Twitter: https://twitter.com/camideasfest #cfi2018

A mechanical picture book, live head casts for the practice of phrenology, stories of the supernatural… this year’s Open Cambridge 2018 becomes curioser and curioser.

Forming a variety of events held across Cambridge on the 14 and 15 September, these themes and many more besides are explored in exhibitions open to the public. Libraries across Cambridge are opening their doors to visitors and showcasing many items which are not usually on display.

Homerton College Library has a fascinating collection of over 10,000 children’s books which collectively span 200 years. In particular, their Victorian mechanical book will enthrall attendees. Published in 1893, the book reproduces the voices of the donkey, lamb, cow, cuckoo, goat, and even the baby, along with coloured illustrations. A Dog’s Dinner Party (1855) is also on display so the public can see a moveable book where the dogs tip their hat to their canine guests across the table. And who wouldn’t want to discover the mystery of the camelopard, a cross between a camel and a leopard as depicted in an early children’s picture book? (The mystery is solved, thanks to the illustration, as the creature can be identified as…a giraffe).

This exhibition celebrates the close tie to education which Homerton College holds, with the college initially concentrating on the study of education and teacher training in its early years, through to the present day, where children’s literature is a subject worthy of study in its own right. Deputy Librarian, Jess Taylor, describes the exhibition as “a heritage snapshot which can be enjoyed by younger visitors as well as those wanting to take a trip down memory lane to their own childhood books.” Curated to be enjoyed visually, the display includes works from the ‘Golden Age’ of illustrators alongside illustrated poetry such as Jabberwocky, interactive books, scary and creepy works, as well as award winners.

Some fascinations developed during childhood never leave us, and Christ’s College Library are holding an exhibition to explore the strange world of the supernatural. Five cases focus on witches, ghosts, fairies, monsters, and mythical beasts. Visitors are treated to an array of works including a 1640 edition of Ovid’s Metamorphoses, Edward Topsell’s Historie of Foure-Footed Beasts (1607), a first edition copy of Mary Shelley’s Frankenstein, and a fourth folio edition of Shakespeare’s works, opened on the witches of Macbeth. People will even hear of the Christ’s College ghost who has been seen wandering morosely around the College gardens.

Another curious practice of our past is phrenology, and the Whipple Library’s event Mind your head promises to both educate and entertain on this curious pseudo-medicine. The library has around 350 items relating to phrenology, most of which were donated by the British Phrenological Society. Along with a range of items including advertising materials, books, flyers, pamphlets, there are live casts of heads on show. These fascinating objects show how the shape of the skull (and therefore brain) was believed to determine certain characteristics. One example was the ultimate French romantic villain, Francois Lacenaire, whose enlarged area above his left ear was believed to indicate a ‘particularly destructive trait’.

Yet these casts also show the darker and less understanding side of phrenology. The ‘Idiot of Amsterdam’ cast most likely captures someone with learning difficulties, and the cast of a substantially enlarged skull probably shows somebody who experienced excess brain fluid – a condition both dangerous and painful. Although phrenology is now largely discredited, it did allow for the development of psychology, and visitors to the Whipple event will be able to get involved with their own diagnostic kit, including a ‘brain hat’.

Don’t miss the hidden treasures at Cambridge Central Library event, where you can watch the book sorter in action and find out what the library in Lion Yard has to offer. Come and listen to Professor Morag Styles speak on picture books, which perfectly complements the Homerton College picture book exhibition (see above). And don’t forget the chance to visit University libraries, such as the Squire Law library and Queens’ College Old Library.

The researchers, from the University of Cambridge, the École Nationale Supérieure des Mines and INSERM in France, implanted the device into the brains of mice, and when the first signals of a seizure were detected, delivered a native brain chemical which stopped the seizure from progressing. The results, reported in the journal Science Advances, could also be applied to other conditions including brain tumours and Parkinson’s disease.

The work represents another advance in the development of soft, flexible electronics that interface well with human tissue. “These thin, organic films do minimal damage in the brain, and their electrical properties are well-suited for these types of applications,” said Professor George Malliaras, the Prince Philip Professor of Technology in Cambridge’s Department of Engineering, who led the research.

While there are many different types of seizures, in most patients with epilepsy, neurons in the brain start firing and signal to neighbouring neurons to fire as well, in a snowball effect that can affect consciousness or motor control. Epilepsy is most commonly treated with anti-epileptic drugs, but these drugs often have serious side effects and they do not prevent seizures in three out of 10 patients.

In the current work, the researchers used a neurotransmitter which acts as the ‘brake’ at the source of the seizure, essentially signalling to the neurons to stop firing and end the seizure. The drug is delivered to the affected region of the brain by a neural probe incorporating a tiny ion pump and electrodes to monitor neural activity.

When the neural signal of a seizure is detected by the electrodes, the ion pump is activated, creating an electric field that moves the drug across an ion exchange membrane and out of the device, a process known as electrophoresis. The amount of drug can be controlled by tuning the strength of the electric field.

“In addition to being able to control exactly when and how much drug is delivered, what is special about this approach is that the drugs come out of the device without any solvent,” said lead author Dr Christopher Proctor, a postdoctoral researcher in the Department of Engineering. “This prevents damage to the surrounding tissue and allows the drugs to interact with the cells immediately outside the device.”

The researchers found that seizures could be prevented with relatively small doses of drug representing less than 1% of the total amount of drug loaded into the device. This means the device should be able to operate for extended periods without needing to be refilled. They also found evidence that the delivered drug, which was in fact a neurotransmitter that is native to the body, was taken up by natural processes in the brain within minutes which, the researchers say, should help reduce side effects from the treatment.

Although early results are promising, the potential treatment would not be available for humans for several years. The researchers next plan to study the longer-term effects of the device in mice.

Malliaras is establishing a new facility at Cambridge which will be able to prototype these specialised devices, which could be used for a range of conditions. Although the device was tested in an animal model of epilepsy, the same technology could potentially be used for other neurological conditions, including the treatment of brain tumours and Parkinson’s disease.

The research was funded by the European Union.

Reference: 
Christopher M. Proctor et al. ‘Electrophoretic drug delivery for seizure control.’ Science Advances (2018). DOI: 10.1126/sciadv.aau1291

In recent decades, exposures to environmental toxic metals such as arsenic, copper, lead, cadmium and mercury, have become a global public health concern. Although often naturally occurring, these contaminants have made their way into water supplies and, via irrigation, into the food chain. For example, in Bangladesh, deep wells were introduced in the Ganges Delta to draw water clear of bacterial and viral pathogens, but this inadvertently led to exposure to toxic metals.

Concern has often focused on the toxicity or carcinogenic properties of the metals, particularly at high doses. However, there is increasing evidence to suggest that heavy metals may have other adverse effects on health – including cardiovascular disease such as heart disease and stroke – even at lower levels of exposure, which might be prevalent in many parts of the world, including the UK and the US.

To interpret the available evidence, a team led by researchers at Cambridge’s Department of Public Health and Primary Care carried out a systematic review and meta-analysis of published studies covering 350,000 unique participants from 37 countries.

The results of the study showed that exposure to arsenic, lead, cadmium and copper – but not mercury – was associated with an increased risk of coronary heart disease and cardiovascular disease.

“It’s clear from our analysis that there’s a possible link between exposure to heavy metals or metalloids and risk of conditions such as heart disease, even at low doses – and the greater the exposure, the greater the risk,” says Dr Rajiv Chowdhury, the study’s first author. “While people shouldn’t be overly worried about any immediate health risk, it should send a message to policymakers that we need to take action to reduce people’s exposure.”

Worldwide, those at greatest exposure of arsenic, lead, cadmium and copper were around 30% to 80% more likely to develop cardiovascular disease than those at lowest exposure.

The report is important, say the researchers, because it highlights the need to tackle this environmental and public health problem, one which disproportionately affects people in low and middle income countries, though may still affect those in higher income countries. Interventions need not be costly, they stress; for example, cheap, scalable technologies (e.g. environmentally-friendly water filters) or behavioural interventions (e.g. rinsing practices of rice and vegetables prior to cooking) are currently being tested to reduce exposures at the household level.

Additionally, in a letter published at the end of June, Dr Chowdhury and colleagues expressed their disappointment that the earlier WHO report by the Independent High-Level Commission on non-communicable diseases published in June did not include exposure to heavy metals as a key contributing factor. Writing in the Lancet, the authors said: “Unfortunately, this globally important report had a major omission: recognising the detrimental role of environmental risk factors, beyond the conventional behavioural factors (tobacco and alcohol use, physical inactivity, and unhealthy diet), in enhancing global NCD burden and health inequality.”

Dr Chowdhury and colleagues recently also received £8.1 million from the UK Research Councils’ Global Challenges Research Fund to set up a long-term programme (called CAPABLE) to further investigate environmental factors of cardiovascular diseases and to help inform preventative strategies.

Reference
1) Chowdhury, R et al. Environmental toxic metal contaminants and cardiovascular risk: a systematic review 1 and meta-analysis of observational studies. BMJ; 30 Aug 2018; DOI:10.1136/bmj.k3310

2) Chowdhury R, et al. Reducing NCDs globally: the under-recognised role of environmental risk factors. The Lancet; 28 June 2018; DOI: 10.1016/S0140-6736(18)31473-9

In many cooperative species, the dominant breeders live longest despite the wear-and-tear of leadership and reproduction.

It has even been suggested these breeders hold the secret of immunity to age-related diseases. Some social insects, such as bees, do have breeders with genetic profiles that delay ageing – but this has never been documented in our fellow mammals.

Scientists from the University of Cambridge have now investigated the lifespans of meerkats: a highly social mammal that lives in groups of up to fifty, where a single dominant couple produce around 90% of the pups.    

The researchers found that the DNA of dominant breeders actually shows signs of accelerated ageing – yet they still consistently outlive the non-breeding subordinates in the group. Their study shows that dominants live an average of 4.4 years compared to subordinates 2.8 years.

This is because meerkat underlings are forced to take the often-fatal risk of leaving the safety of the group to find breeding opportunities, say scientists. Dominants rarely tolerate rival breeders, and violently eject subordinates from the group if they feel threatened.

On reaching the top of the social pecking order, however, meerkats remain ensconced within the group. The study shows an average subordinate spends more than six days each year in the wilderness, with this figure rising year-on-year. Dominant breeders are typically absent for under two hours per year.

“Dominant meerkats typically die due to internal stresses on their bodies, resulting in gradual, predictable declines until death. In humans we might describe this as ‘natural causes’,” said Dr Dominic Cram from Cambridge’s Department of Zoology, lead author of the study published today in Current Biology. 

“Subordinate meerkats die due to sudden, unpredictable circumstances such as exposure to predators, killing them instantly. A meerkat’s place within the social group shapes the mortality risks it faces,” he said.

“The secret of long life for meerkats is not to battle the inevitable declines of ageing, but to be the ruler of your community, profiting from social support and cracking down on would-be rivals.”

Cram conducted the research as part of the Kalahari Meerkat Project: a long-term study of social behavior and ecology, run for over twenty years at the University of Cambridge by Professor Tim Clutton-Brock – a leading figure in the study of mammal societies.

The project has helped train generations of zoologists through the observation of generations of meerkats, resulting in a wide range of data on the life histories of over 3000 meerkat individuals in over 100 groups.

The team collected blood samples from the meerkats, and measured DNA sections called telomeres that help protect DNA from damage – much like the plastic caps on shoe-laces. As they erode over time, the chance of unravelling increases, so the length of telomeres can be used to estimate “biological age”.

While the telomeres of subordinate meerkats remained stable, dominant telomeres shrunk by a third in just 18 months – suggesting accelerated ageing caused by the toils of raising young and fending off rivals.

Yet the dominant meerkats still lived an average of 60% longer than subordinates, as the lower ranking meerkats were increasingly forced to risk more and more time outside the group as they grew older.

“Each year the subordinates spend over triple the amount of time outside the group as the previous year, reaching a peak of 35 days per year, or 10% of their time, outside the social group,” said Cram.

For subordinate males, all females in the group are their sisters or mother, so they must court females away from the group to avoid inbreeding. Subordinate females are bullied and chased away by the dominant when they become a reproductive rival.

Of all those that leave, some return – or try to – after a few days or weeks. A lucky few start their own group and become dominant breeders. Many are never seen again.

“Within a group, a sentinel always keeps look-out and sounds the alarm, allowing the meerkats to flee into burrows or bolt-holes. Each meerkat takes a turn on sentinel duty,” said Cram.

“Away from the group there is no early warning system, and meerkats are easy prey for eagles, goshawks and caracal. Letting down their guard to dig for food is too risky, so many starve for fear of being eaten.”

“Lone meerkats have even been known to be torn apart by members of a rival group. It’s a dangerous world for a solo meerkat.”

Tributes have been paid to Sir James Mirrlees (1936-2018), Emeritus Professor of Political Economy at Cambridge and a Fellow of Trinity College, who also taught at Oxford and in America, and played an important role at the Chinese University of Hong Kong.

His wife Patricia said: "Jim was brilliant and yet he was modest and lived simply. 

"He gave generously of his time and knowledge as a teacher and supervisor in Oxford and Cambridge and as the Master of Morningside College.

"He was deeply loved and respected and will be sorely missed. 

"His great life is over, but Jim will live on through his work and those he inspired."

Professor Sir Partha Dasgupta, Frank Ramsey Professor Emeritus of Economics at Cambridge, Fellow of St John’s and Honorary Fellow of Trinity, said: "James Mirrlees’ moral seriousness, allied to dazzling mathematical skills and an unerring eye for building minimalist economic models were reflected in some half-dozen articles that together constructed the theoretical foundations of public economics.

"To those of us who were privileged to observe his academic life at close quarters, it was also a source of amazement that he found it entirely right and proper to spend more time on his many students than on his own writings. He was unquestionably one of the most influential economists of the final quarter of the last century."

In 1996 Sir James won the Nobel Prize in Economic Sciences with Professor William Vickrey, of Columbia University, for their research on the economic theory of incentives when information is incomplete or asymmetric. Sir James was knighted in 1997.

Professor Sir Richard Blundell, Director of the Institute for Fiscal Studies and Ricardo Professor of Political Economy at UCL, said: "Jim Mirrlees was a remarkable and hugely influential economist. He revolutionised the way we think about incentives and inequality in policy design. Most notably in the area of tax design but with far reaching implications across many areas of economics.

"Understanding incentives and behaviour under asymmetric information remains at the heart of modern economics and is as live an issue now as it was when Mirrlees was awarded the Nobel Prize more than 20 years ago.

"A wonderfully kind person and a delight to work with, he will be deeply missed by us all."

Born in Scotland and educated at the University of Edinburgh and then Trinity College, Sir James came to economics by way of mathematics, and an interest in philosophy. He was a Wrangler during his mathematics’ degree at Trinity before pursuing a PhD in economics.

Writing about his life for the Nobel Foundation, he said: ‘…it was indeed economics I wanted to do, because I kept discussing it with economist friends, and they didn’t make sense to me; and because poverty in what were then called the underdeveloped countries, seemed to me what really mattered in the world, and that meant economics.’

Sir Richard said: "Although much of his published work was on the development of fundamental new theory, the implications for economic policy were never far from his mind."

Working with the Institute of Fiscal Studies, Sir James chaired the Mirrlees Review, which brought together a group of international experts to identify the characteristics of a good tax system for developed countries, to assess to what extent the UK tax system met those characteristics, and to recommend reforms to that end. The Mirrlees Review, published in 2011, remains an internationally influential plan for comprehensive tax reform.

Sir James served as President of the Econometric Society and the Royal Economic Society, and was elected a Fellow of the British Academy and an Honorary Fellow of the Royal Society of Edinburgh.

He was Visiting Professor at MIT, the University of California, Berkeley, and at Yale. Between 1968 and 1995 he was Edgeworth Professor of Economics at the University of Oxford and a Fellow of Nuffield College. He returned to Cambridge as Professor of Political Economy, a position he held until retirement in 2003.

His interest in Chinese economic development led to his appointment as Distinguished Professor-at-Large at the Chinese University of Hong Kong, where he was also Master of Morningside College from 2009.

There will be a funeral on Friday 14 September. A date for a Memorial Service in Trinity College Chapel will be announced in due course.

Photosynthesis is the process plants use to convert sunlight into energy. Oxygen is produced as a by-product of photosynthesis when the water absorbed by plants is ‘split’. It is one of the most important reactions on the planet because it is the source of nearly all of the world’s oxygen. Hydrogen which is produced when the water is split could potentially be a green and unlimited source of renewable energy. 

A new study, led by academics at the University of Cambridge, used semi-artificial photosynthesis to explore new ways to produce and store solar energy. They used natural sunlight to convert water into hydrogen and oxygen using a mixture of biological components and manmade technologies.

The research could now be used to revolutionise the systems used for renewable energy production. A new paper, published in Nature Energy, outlines how academics at the Reisner Laboratory in Cambridge's Department of Chemistry developed their platform to achieve unassisted solar-driven water-splitting.

Their method also managed to absorb more solar light than natural photosynthesis.

Katarzyna Sokół, first author and PhD student at St John’s College, said: “Natural photosynthesis is not efficient because it has evolved merely to survive so it makes the bare minimum amount of energy needed – around 1-2 per cent of what it could potentially convert and store.”

Artificial photosynthesis has been around for decades but it has not yet been successfully used to create renewable energy because it relies on the use of catalysts, which are often expensive and toxic. This means it can’t yet be used to scale up findings to an industrial level.

The Cambridge research is part of the emerging field of semi-artificial photosynthesis which aims to overcome the limitations of fully artificial photosynthesis by using enzymes to create the desired reaction.

Sokół and the team of researchers not only improved on the amount of energy produced and stored, they managed to reactivate a process in the algae that has been dormant for millennia.

She explained: “Hydrogenase is an enzyme present in algae that is capable of reducing protons into hydrogen. During evolution, this process has been deactivated because it wasn’t necessary for survival but we successfully managed to bypass the inactivity to achieve the reaction we wanted – splitting water into hydrogen and oxygen.”

Sokół hopes the findings will enable new innovative model systems for solar energy conversion to be developed.

She added: “It’s exciting that we can selectively choose the processes we want, and achieve the reaction we want which is inaccessible in nature. This could be a great platform for developing solar technologies. The approach could be used to couple other reactions together to see what can be done, learn from these reactions and then build synthetic, more robust pieces of solar energy technology.”

This model is the first to successfully use hydrogenase and photosystem II to create semi-artificial photosynthesis driven purely by solar power.

Dr Erwin Reisner, Head of the Reisner Laboratory, a Fellow of St John’s College, University of Cambridge, and one of the paper’s authors described the research as a ‘milestone’.

He explained: “This work overcomes many difficult challenges associated with the integration of biological and organic components into inorganic materials for the assembly of semi-artificial devices and opens up a toolbox for developing future systems for solar energy conversion.”

Reference: 
Katarzyna P. Sokół et al. 'Bias-free photoelectrochemical water splitting with photosystem II on a dye-sensitized photoanode wired to hydrogenase.' Nature Energy (2018). DOI: 10.1038/s41560-018-0232-y

​Originally published on the St John's College website. 

The mentoring of junior colleagues can reduce anxiety and improve the mental health of the mentors themselves in high-pressure occupations, concludes a new study co-authored at Cambridge Judge Business School involving an English police force.

While previous research had indicated that the anxiety of mentees can be reduced through the guidance of more senior mentors, the new study finds that imparting knowledge and experience can also help mentors by making their jobs more rewarding.

“We found that mentoring relationships provide a unique context for mentors to discuss and normalise their concerns, to share ideas for managing anxieties, and to find more meaning in their work,” concludes the study, published in the Journal of Vocational Behavior.

“Mentoring relationships appeared to provide an organisational mechanism to prompt supervisor and colleague interactions, which in turn facilitated a reduction in the mentors’ anxiety.”

In England alone, mental illness accounts for annual expenditure on healthcare of £14 billion and a reduction in gross domestic product of £52 billion owing to people unable to work to their full capacity.

Policing was chosen as an appropriate setting to study how mentoring can reduce anxiety in occupations that play important social roles, including the medical profession and the military – roles that require mental strength in challenging situations coupled with political pressure to become more efficient. The study follows a mentoring programme that was rolled out at one of 43 territory-based police forces in England and Wales since 2013.

Despite the pressures of their roles – including threats, abuse, snap decisions and the risk of death – police officers tend not to seek support from other officers, including more senior colleagues, to avoid “negative stigma” associated with mental health disorders. Mentoring can help fill this void, the study says.

“The study suggests that a relatively inexpensive practice such as mentoring can help reduce anxiety among both senior and junior staff, and this could help organisations address the serious and costly workplace issues of anxiety and mental health,” says study co-author Dr Thomas Roulet, University Senior Lecturer in Organisation Theory at Cambridge Judge Business School. “While the study focused on high-stress roles in the public eye, we believe that the findings may also apply to other occupations that also have anxiety-provoking pressures.”

The study is co-authored by Dr Michael Gill of Said Business School at Oxford University and Chief Inspector Stephen Kerridge of the Cambridgeshire Constabulary.

Excerpts of interviews with mentors and mentees indicated that it was beneficial for people in such busy and often frantic jobs as policing to have an opportunity to be “listened to” and to take note of the fact that “we’ve all gone through” certain work experiences.

“Mentoring provided reassurance to the mentors by illuminating how other, often junior officers also experience anxiety thereby normalising their own experiences,” the study says. “By acknowledging that anxieties are common, both the mentees and mentors in this study appeared to be more comfortable discussing such issues and therefore in developing different coping mechanisms.”

Reference: 
Michael J. Gill et al. 'Mentoring for mental health: A mixed-method study of the benefits of formal mentoring programmes in the English police force.' Journal Of Vocational Behavior (2018). DOI: 10.1016/j.jvb.2018.08.005

Originally published on the Cambridge Judge Business School website. 

The company, Cambridge Heartwear, hopes to use its wireless monitor to improve the detection of irregular and dangerous heart rhythms and reduce the impact of stroke and stroke-related mortality and morbidity, which affects 120,000 people in the UK each year.A Cambridge start-up has developed a low-cost next-generation wearable heart and cardiovascular function monitor which uses AI to diagnose heart rhythm and respiratory problems in real time. 

Professor Roberto Cipolla from Cambridge’s Department of Engineering met cardiologist and clinical academic Dr Rameen Shakur in 2015, a year after Roberto’s father had died of a stroke. Their ongoing research collaboration has now led to the formation of Cambridge Heartwear, a company based on the Cambridge Science Park.

The company’s device, called Heartsense, includes a multiple lead ECG, oxygen sensing, temperature and tracking device which can be comfortably worn by patients for early screening. Sensors are enclosed in a robust waterproof casing, and the data produced is far more sensitive than that from current single lead wearable devices, as the development team have used their knowledge of clinical anatomy and electrophysiology to place leads for maximal signal output.

This data is wirelessly streamed in real time to the cloud where adaptive AI algorithms are able to identify clinically relevant irregular and dangerous rhythms just as a physician would. The device incorporates multiple independent sensors, in order to produce more specific and sensitive data than current heart monitors can provide.

The research challenge was to produce algorithms that can learn from a limited amount of supervision from the cardiologist. “Our aim was not to replace the cardiologist, but to give them diagnostic support in real time,” said Cipolla.

To encourage the adoption by clinicians the team ensured that the output of the AI algorithms also included the information commonly used by a cardiologist. “This was not necessary for the final diagnosis but made the system a little more understandable and explainable than typical Deep Learning systems, which are still thought of as black boxes,” said Cipolla.  

NHS figures suggest atrial fibrillation (AF), the most common heart rhythm disturbance encountered by doctors, affects in excess of one million people across the UK. According to national and international data, more than 80% of people who either die or are left with severe neurological deficits following a stroke had an irregular heartbeat as the underlying cause. However, irregular heartbeat is often diagnosed only after a person has had a stroke.

There are more than 100,000 strokes in the UK every year, and it is the fourth biggest killer in the in the UK, with more than 23,000 deaths last year. The NHS spends £2.5 billion annually on neurological treatment and rehabilitation for stroke patients.

“It makes sense to pick up AF before someone has a stroke and put preventative treatment in place,” said Shakur, who was formerly a Wellcome Trust Clinical Fellow at Cambridge and is now based at MIT. “Unfortunately, the technology and clinical care systems we currently have in place aren’t really doing this.”

Heart rhythms are currently measured by an electrocardiogram (ECG). To use an ECG as someone is going about their daily business, rather than in a GP surgery, a device called a Holter monitor is used. This requires fixing 12 leads to the patient’s chest and carrying the cumbersome device around for 24 hours.

It can take as long as four to six weeks from the time when a patient is referred by their GP to when the data from the Holter monitor is analysed and an irregular heartbeat is detected or not. Additionally, a Holter monitor costs as much as £2000.

“If you’re wearing an ECG over a long period of time, you’re collecting a huge amount of data,” said Shakur. “Finding an irregularity among all the normal rhythms can be like looking for a needle in a haystack. I wanted to automate this process, helping the patient to get a diagnosis and start on treatment.”

To solve this problem, Shakur began collaborating with Cipolla, a world leader in computer vision and real-world applications, and students from the Department of Engineering. The collaboration led to the founding of Cambridge Heartwear in 2017 and the development of the unique device and some powerful algorithms that can automatically interpret ECG data, which have an accuracy level in excess of 95%.

In 2017, the company secured funding to build and test 100 prototypes of the new heart monitor and to extend its AI capability. The Royal College of Art was also helped in the ergonomic design of the device. Heartsense will cost substantially less than a Holter monitor.

Clinical trials in Lancashire, UK have begun with patients enrolled from the primary care setting. 

Inset image: (L-R) Roberto Cipolla, Rameen Shakur, James Charles

Agriculture that appears to be more eco-friendly but uses more land may actually have greater environmental costs per unit of food than “high-yield” farming that uses less land, a new study has found.

There is mounting evidence that the best way to meet rising food demand while conserving biodiversity is to wring as much food as sustainably possible from the land we do farm, so that more natural habitats can be “spared the plough”.   

However, this involves intensive farming techniques thought to create disproportionate levels of pollution, water scarcity and soil erosion. Now, a study published today in the journal Nature Sustainability shows this is not necessarily the case.

Scientists have put together measures for some of the major “externalities” – such as greenhouse gas emission, fertiliser and water use – generated by high- and low-yield farming systems, and compared the environmental costs of producing a given amount of food in different ways.

Previous research compared these costs by land area. As high-yield farming needs less land to produce the same quantity of food, the study’s authors say this approach overestimates its environmental impact.

Their results from four major agricultural sectors suggest that, contrary to many people's perceptions, more intensive agriculture that uses less land may also produce fewer pollutants, cause less soil loss and consume less water.

However, the team behind the study, led by scientists from the University of Cambridge, caution that if higher yields are simply used to increase profit or lower prices, they will only accelerate the extinction crisis we are already seeing.  

“Agriculture is the most significant cause of biodiversity loss on the planet,” said study lead author Andrew Balmford, Professor of Conservation Science from Cambridge’s Department of Zoology. “Habitats are continuing to be cleared to make way for farmland, leaving ever less space for wildlife.”

“Our results suggest that high-yield farming could be harnessed to meet the growing demand for food without destroying more of the natural world. However, if we are to avert mass extinction it is vital that land-efficient agriculture is linked to more wilderness being spared the plough.”

The Cambridge scientists conducted the study with a research team from 17 organisations across the UK and around the globe, including colleagues from Poland, Brazil, Australia, Mexico and Colombia.

The study analysed information from hundreds of investigations into four vast food sectors, accounting for large percentages of the global output for each product: Asian paddy rice (90%), European wheat (33%), Latin American beef (23%), and European dairy (53%).

Examples of high-yield strategies include enhanced pasture systems and livestock breeds in beef production, use of chemical fertilizer on crops, and keeping dairy cows indoors for longer.

The scientists found data to be limited, and say more research is urgently needed on the environmental cost of different farming systems. Nevertheless, results suggest many high-yield systems are less ecologically damaging and, crucially, use much less land. 

For example, in field trials, inorganic nitrogen boosted yields with little to no greenhouse gas “penalty” and lower water use per tonne of rice. Per tonne of beef, the team found greenhouse gas emissions could be halved in some systems where yields are boosted by adding trees to provide shade and forage for cattle.

The study only looked at organic farming in the European dairy sector, but found that – for the same amount of milk – organic systems caused at least one third more soil loss, and take up twice as much land, as conventional dairy farming.

Co-author Professor Phil Garnsworthy from the University of Nottingham, who led the dairy team, said: “Across all dairy systems we find that higher milk yield per unit of land generally leads to greater biological and economic efficiency of production. Dairy farmers should welcome the news that more efficient systems have lower environmental impact.”

Conservation expert and co-author Dr David Edwards, from the University of Sheffield, said: “Organic systems are often considered to be far more environmentally friendly than conventional farming, but our work suggested the opposite. By using more land to produce the same yield, organic may ultimately accrue larger environmental costs.”

The study authors say that high-yield farming must be combined with mechanisms that limit agricultural expansion if they are to have any environmental benefit. These could include strict land-use zoning and restructured rural subsidies.

“These results add to the evidence that sparing natural habitats by using high-yield farming to produce food is the least bad way forward,” added Balmford.

“Where agriculture is heavily subsidised, public payments could be contingent on higher food yields from land already being farmed, while other land is taken out of production and restored as natural habitat, for wildlife and carbon or floodwater storage.”

Fifty leading engineers from the UK and around the world have been elected as Fellows of the Royal Academy of Engineering in recognition of their outstanding and continuing contributions to the profession.

The 50 new Fellows will be formally admitted to the Academy at its AGM in London today, in addition to four International Fellows and one Honorary Fellow, who will add their expertise to the Fellowship of nearly 1,600 world-leading engineers from both industry and academia.

The three Cambridge researchers announced today as new Fellows are Professor Judith Driscoll from the Department of Materials Science & Metallurgy, Professor Andy Neely, Pro-Vice-Chancellor for Enterprise and Business Relations and former Head of the Institute of Manufacturing (IfM), and Professor Robin Langley from the Department of Engineering. 

Professor Judith Driscoll has made many technologically important contributions. She was recently awarded the Royal Academy of Engineering Armourers and Brasiers Prize for innovating nano-structured superconducting thin films. This integrates concepts from several disciplines (including composite theory and electronic engineering) and all superconductor wire manufacturers now use the pinning methodologies she developed. Some also use a liquid assisted processing methodology she initiated, which enables faster and more cost-effective wire production. Applications include generators, motors, energy storage and high-field magnets. Other important advances include developments in magnetics, ionics and ferroelectrics.  

Professor Andy Neely is widely recognised for his work on the design and deployment of manufacturing performance indicators, as well as the servitisation of manufacturing – the tendency for manufacturing firms to sell services and solutions rather than products. He is founding director of the Cambridge Service Alliance and leads the Centre for Digital Built Britain.

Professor Robin Langley is distinguished for his work in acoustics and mechanical vibration to elucidate the complex dynamics of aerospace, automotive, offshore and marine structures. He has made preeminent contributions to statistical methods of vibration theory and his methods and software are widely used by practitioners in this field. He has held a range of senior leadership roles in the academic sector, promoting research and education in engineering and supporting the career development of his academic colleagues. 

Professor Dame Ann Dowling OM DBE FREng FRS, President of the Royal Academy of Engineering, said: “I am delighted to welcome all our new Fellows to the Academy - together they epitomise the very best of UK engineering. Representing the country’s most innovative and creative minds from both academia and industry, the achievements of our new Fellows highlight the critical role engineering has in addressing major societal challenges and ensuring our readiness for the future. We are very much looking forward to working with them as we continue to fulfil our vision of engineering at the heart of a sustainable and prosperous society.”  

Influenza is one of the main infectious diseases in humans. Seasonal influenza viruses account for about 650,000 deaths per year, whereas pandemic strains such as the 1918 H1N1 pandemic virus have been linked to 50-100 million deaths worldwide. Highly pathogenic avian influenza viruses such as the H5N1 and H7N9 strains have a mortality rate of about 50% in humans.

The reasons for difference in disease severity and lethality caused by seasonal influenza viruses on the one hand, and pandemic and highly pathogenic avian influenza viruses on the other hand is still poorly understood. Previous research has indicated that in infections with the 1918 pandemic virus or infections with an H5N1 avian virus, a powerful immune response is established that leads to death.

This led Dr Aartjan te Velthuis of the University of Cambridge and his colleagues Prof Ervin Fodor, Dr Josh Long and Dr David Bauer of the University of Oxford, to ask what viral molecule can trigger this powerful immune response.

The British groups first looked to how viruses are detected by the cell. Normally, an infected cell spots the presence of a virus by sensing the genetic material of the virus, RNA in the case of flu.

Work by Dr Richard Randall, a co-author on the manuscript from the University of St Andrews, has shown that influenza viruses are good at hiding their RNA. This observation prompted te Velthuis and his colleagues to look for flu RNA that the virus was not able to hide from the cellular pathogen sensing system. What they found was truncated pieces of the viral genome that the virus had produced in error. The researchers called these pieces mini viral RNAs.

Fodor and his colleagues next investigated whether different influenza viruses produce mini viral RNAs at different frequencies and whether there was a link with the strong innate immune response that, for instance, the 1918 pandemic virus induces.

A combination of in vitro and in vivo experiments performed at Oxford and Cambridge, as well as by collaborators Leo Poon of the University of Hong Kong, Debby van Riel of the Erasmus Medical Centre, and Emmie de Wit of the Rocky Mountain Laboratories, revealed indeed a strong correlation between the ability of an influenza virus to generate mini viral RNAs and the amount of inflammation and cell death the virus infection caused.

“We think it is a significant breakthrough and that it is particularly exciting that we are finding this factor a hundred years after the 1918 pandemic,” said Dr te Velthuis.

The research groups are now continuing their efforts to investigate whether there is a causal link between influenza virus mortality and the production of mini viral RNAs. Together with their latest work, these efforts may help us understand better how influenza viruses cause disease, how we can identify dangerous influenza viruses, and how to develop new antivirals against influenza virus infections.

The work was funded by the Wellcome Trust, Royal Society, Medical Research Council, NIH, and the Netherlands Organization for Scientific Research.

The Migration Advisory Committee report published today puts forward strong evidence of the unequivocally positive contribution that EEA nationals make to the UK’s economy, culture and society. These contributions are felt in all aspects of the University of Cambridge’s life and operations, and are central to the University’s global success.

As we stated in our response to the Migration Advisory Committee, the cumbersome Tier 2 immigration route acts as a deterrent to recruiting the staff we need to fulfill the University’s mission. Extending it to EEA nationals would further harm the UK’s competitiveness.

The University relies on a wide range of talents and skill sets, from specialist technicians to professorial roles. Simply put, the recommendations from the MAC report published today, if enacted, would not enable us to access the talent we need to maintain and enhance our place in an increasingly competitive higher education sector globally.

Now is a good moment for a comprehensive review of the UK’s immigration policies.  In light of the overwhelming evidence of the positive contribution of EEA nationals to the UK, I  call on the Government to engage with us and others to develop an immigration system that supports the UK’s research base and innovation capabilities.

The Rising Path is part of the Garden’s Understanding Plant Diversity Project, a three year project supported by The Monument Trust, which aims to revitalise the contemporary relevance of the Garden’s Systematic Beds for researchers, teachers and visitors by exploring how plant diversity is identified and organised – the science of plant taxonomy.

Professor Beverley Glover, Director of the Botanic Garden, said: “We are thrilled to be opening the Rising Path to the public. This innovative structure is a key part of an ongoing project to re-examine, re-interpret and re-display our Systematic Beds which will help visitors, students and scientists to understand more about plants, how they are related, and why this is so important for science.” 

Rising Path Project Manger, Juliet Day, said: “Observation is the cornerstone of all scientific enquiry and plants are full of shapes, patterns, numbers, colours, textures, symmetry, scents and tastes to discover. We have developed the Rising Path and created interpretation displays to encourage visitors of all ages to explore the Systematic Beds and enjoy looking more closely at plants.”

The Rising Path leads to a viewing platform where visitors will be able to see the full extent and layout of the Systematic Beds from a 3m high vantage point. Rest points along the path highlight the innovations that allowed plants to leave the water for life on land and to proliferate into the 400,000 species known today. 

At ground level, an interpretation hub expands on the twin educational purpose of the Systematic Beds: how to look at plants, and how to organise those plants in order to provide a robust framework for effective research and communication. 

Added Glover “For thousands of years, humans have grouped plants into families based on observation made using the naked eye. Today, scientists also study the DNA of plants to determine relationships. Changes in scientific understanding pose interesting challenges for a Garden that seeks to be both guardian of a historic landscape and relevant to contemporary research.” 

The Systematic Beds occupy nearly three acres of CUBG and are of global heritage significance. They were designed in 1845 by CUBG’s first Curator, Andrew Murray, and their design uniquely translates the leading botanic text book of the time by Augustin de Candolle into a display on the ground to represent and teach plant taxonomy - the science of identifying and classifying plant species. 

The Understanding Plant Diversity project, which includes the Rising Path, seeks to ensure the Systematic Beds remain a useful teaching tool in the modern world. When renovation is complete in 2019, the Systematic Beds will represent 1,600 plant species belonging to about 78 families dispersed across 119 beds.

The building houses the Centre for Misfolding Diseases, a world-leading research facility focused on the misfolding of proteins in human cells - a phenomenon that causes a number of disorders including Alzheimer’s, Parkinson’s, Huntington’s and Motor Neurone Diseases.

The building has been funded by £17.6 million from Research England’s UK Research Partnership Investment Fund (UKRPIF), as well as with contributions from Elan Pharmaceuticals and AstraZeneca.

Among the philanthropic contributions to the project is a donation of £5 million from Cambridge alumnus Derek Finlay in memory of his wife, Una, who died in May 2016 after a long struggle with Alzheimer’s disease. The first-floor laboratory is named the Una Finlay Laboratory in her memory and as the name-plaque was unveiled, Mr Finlay said: “This is a special and very poignant day for myself and my family. This building will enable world-class research that will speed up the search for ways to delay, ameliorate and – I believe – ultimately abolish these dreadful neurodegenerative diseases.”

“The research carried out in this new facility has the potential to affect millions of lives around the world for the better,” said Cambridge Vice-Chancellor Professor Stephen Toope, who opened the building today. “Through collaboration and the sharing of ideas, our research teams will work to find the keys that unlock the mysteries of neurodegenerative disorders, one of the greatest health problems of our age.”

A 2015 report suggested that by 2030, there will be 75 million people worldwide living with Alzheimer’s disease. While the number of cases of Alzheimer’s diseases and other neurodegenerative disorders continues to rise, so too do the costs to society, both economic and emotional.

The Centre for Misfolding Diseases is co-directed by Professor Sir Christopher Dobson, Professor Tuomas Knowles and Professor Michele Vendruscolo, three world leaders in their fields who have been studying the molecular origins of neurodegenerative diseases.

“This building will for the first time bring together a large number of scientists from different disciplines who are dedicated to establishing the molecular basis of neurodegenerative disorders and to identifying new ways for treating or preventing these debilitating conditions,” said Dobson.

“The treatment of neurodegenerative disorders represents a major challenge, requiring both the development of innovative biophysical approaches and their translation into diagnostic and therapeutic tools,” said Vendruscolo. “With this new building, we have created favourable conditions to combine these two steps.”

“This facility will be a crucial element in helping us to tackle the challenge of understanding the molecular mechanisms of dementia and develop effective ways to counteract them,” said Knowles.

The new building is also home to a Chemistry of Health Incubator, which will enable closer collaborations between researchers and industry and host spin-out companies in order to increase the rate at which scientific discoveries are translated into new therapies. The new incubator is the first in Cambridge to be directly integrated into a University department, and will provide the resources and complementary know-how required to ensure that fundamental research is ultimately used to develop new treatments for patients. The first spin-out company to move into the Incubator will be Wren Therapeutics, which is based on a ground-breaking drug discovery method for neurodegenerative disorders developed at the Centre for Misfolding Diseases.

These questions and many more on subjects ranging from the future of capitalism and whether marriage is healthy to how democracy ends will be discussed at this year’s Cambridge Festival of Ideas, which opens for bookings today.

The Festival, which runs from 15 to 28 October, includes over 200 events and exhibitions. Speakers include bestselling author Tara Westover, former Archbishop of Canterbury Rowan Williams, Professor David Runciman, Fiona Mactaggart from the Fawcett Society and Professor David Reynolds.

Top picks for this year’s Festival include:

From politics: Professor David Runciman will speak about the threats to democracy in the 21st century in How Democracy Ends.

From economics: in Trade wars: deal or no deal an expert panel will discuss what the likely impact of trade wars is and how the tension between protectionism and free trade has played out in history.

From history: Forms of extreme protest in the post-war West explores two very different forms of extreme protest: violent protest cultures within ethno-separatist movements and two forms of extreme religious protests as part of the HIV/AIDS movement in Britain: the Catholic AIDS Link and the Sisters of Perpetual Indulgence.

From social affairs: marriage comes under the spotlight in the discussion Does marriage make us healthier? which brings together two historians, a psychologist, a scientist and a relationship counsellor to discuss the ways individuals have defined bodily and emotional health and its complex relationship with marriage in the past and present.

From technology: Shining a light on the dark web explores the dangers of the dark web, including how anonymous users can purchase illegal firearms and drugs on this hidden part of the internet.  

From health: Improving our diets: more freedom or more control? debates whether we should be free to choose what we eat or whether there should be more state control.

A number of events deal with some of today’s most complex religious issues.

In Apocalyptic terrorism: taming the pale horse Dr Justin Meggitt from the Faculty of Divinity will focus on contemporary movements that have been associated with acts of terrorism, such as Aum Shinrikyo, ISIS and various environmental and white supremacist groups.

Dr Meggitt says: “Most apocalyptic groups share the following ideas: that the world is ruled by evil, that a special group possesses this knowledge, an authoritative text or figure discloses that the way the world appears to be is not the case, that the way things are is about to be shattered by a cataclysmic event and that those in the know will have a special role in these events. It is important to emphasise that not all apocalyptic groups believe that they have a role in bringing about this cataclysm or, if they do, this is necessarily a violent role.

“Apocalyptic movements are often misunderstood. They are not necessarily violent. In fact, historically, some have been radical pacifists. However, they are often depicted as solely destructive or dismissed out of hand. A significant proportion of the world’s population belong to movements that are apocalyptic, so we cannot afford to do this, and many people in the past were motivated by such ideas, and we do them a disservice if we do not try to make sense of the way they thought about the world.”

In Rethinking religious fundamentalism, Professor Kim Knott, Lancaster University, Ed Kessler MBE, Woolf Institute, Cambridge, and Tobias Müller, Woolf Institute and POLIS, University of Cambridge, discuss why fundamentalist beliefs and practices are so attractive to some, how fundamentalism relates to mainstream interpretations of the same religion and how we should distinguish between fundamentalism, extremism, radicalism and orthodoxy. They will focus on shared characteristics such as the desire to return to a golden age, the importance of charismatic leadership and the influence of globalisation while pointing out differences. 15 October

Other events linked to religions include:

The mystery of mythical seizures: This panel reflects on mystical experiences during epileptic seizures and what they can teach us about empathy, personal reflection and how different traditions of faith or non-faith can intersect in big questions about the nature of personal experience. It includes experts on the psychology of religion and people who have had mystical seizures. 18 October

What have the angels ever done for us? Angels are a nearly ubiquitous aspect of many world religions. They continue to be widely represented in popular literature, theatre, cinema, radio, television and music. Yet many doubt the intelligibility of the angels, although they are among the most exciting and least known topics in theology. This discussion panel will address who and what angels represent in religion and culture and whether they exist. 19 October

What is extreme? Definitional issues in the Government’s Prevent counter-terrorism strategy? Ryan Hill from Anglia Ruskin University discusses the Government’s use of the term non-violent extremism. 27 October

The Festival sponsors and partners are St John’s College, Anglia Ruskin University, RAND Europe, University of Cambridge Museums and Botanic Garden, Cambridge Junction and Cambridge University Press. The Festival media partners are BBC Radio Cambridgeshire and Cambridge Independent.

*To book online go to www.cam.ac.uk/festivalofideas or ring the booking line on 01223 766766.

The researchers, led by the University of Cambridge, applied an experimental gene therapy treatment in mice and were able to successfully target and eliminate the damaged DNA in mitochondria which causes the devastating conditions.

Their results, published in the journal Nature Medicine, could provide a practical route to treating patients with these diseases and may provide a future alternative to mitochondrial replacement therapy, or ‘three-parent IVF’. This is the first time programmable genome engineering tools have been used inside a living animal, resulting in such significant modification of mitochondrial DNA.

Mitochondria are the powerhouses inside our cells, producing energy and carrying their own DNA. They are inherited from a person’s mother via the egg, but if they are damaged, it can result in a serious mitochondrial disease. For example, MELAS Syndrome is a severe multi-system disorder causing progressive loss of mental and movement abilities, which usually becomes apparent in early childhood.

There are typically about 1000 copies of mitochondrial DNA per cell, and the percentage of these that are damaged, or mutated, will determine whether a person will suffer from mitochondrial disease or not. Usually, more than 60% of the mitochondrial DNA molecules in a cell need to be mutated for the disease to emerge, and the more mutated mitochondrial DNA a person has, the more severe their disease will be. Conversely, if the percentage of mutated DNA can be reduced, the disease could potentially be treated.

Mitochondrial diseases are currently incurable, although a new IVF technique of mitochondrial transfer gives families affected by mitochondrial disease the chance of having healthy children – removing affected mitochondria from an egg or embryo and replacing them with healthy ones from a donor.

“Mitochondrial replacement therapy is a promising approach to prevent transmission of mitochondrial diseases, however, as the vast majority of mitochondrial diseases have no family history, this approach might not actually reduce the proportion of mitochondrial disease in the population,” said Dr Payam Gammage, a postdoctoral researcher in the MRC Mitochondrial Biology Unit, and the paper’s first author.

“One idea for treating these devastating diseases is to reduce the amount of mutated mitochondrial DNA by selectively destroying the mutated DNA, and allowing healthy DNA to take its place,” said Dr Michal Minczuk, also from the Medical Research Council (MRC) Mitochondrial Biology Unit, and the study’s senior author.

To test an experimental gene therapy treatment, which has so far only been tested in human cells grown in petri dishes in a lab, the researchers used a mouse model of mitochondrial disease that has the same mutation as some human patients.

The gene therapy treatment, known as the mitochondrially targeted zinc finger-nuclease, or mtZFN, recognises and then eliminates the mutant mitochondrial DNA, based on the DNA sequence differences between healthy and mutant mitochondrial DNA. As cells generally maintain a stable number of mitochondrial DNA copies, the mutated copies that are eliminated are replaced with healthy copies, leading to a decrease in the mitochondrial mutation burden that results in improved mitochondrial function.

The treatment was delivered into the bloodstream of the mouse using a modified virus, which is then mostly taken up by heart cells. The researchers found that the treatment specifically eliminates the mutated mitochondrial DNA, and resulted in measures of heart metabolism improving.

Following on from these results, the researchers hope to take this gene therapy approach through clinical trials, in the hope of producing an effective treatment for mitochondrial diseases.

This work was supported by the Medical Research Council and was performed in collaboration with Sangamo Therapeutics and the Max Planck Institute for Biology of Ageing in Cologne.

Reference:
Payam A. Gammage et al. ‘Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.’ Nature Medicine (2018). DOI: 10.1038/s41591-018-0165-9.

Academics at the University of Cambridge and at Lund University in Sweden have devised the first strategy to ‘go after’ the cause of the devastating disease, which could eventually lead to the development of new drugs to treat dementia. Their findings are reported in the journal PNAS.

“This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease - has been proposed,” said Professor Michele Vendruscolo from Cambridge’s Department of Chemistry, the paper’s senior author. “Until very recently scientists couldn’t agree on what the cause was so we didn’t have a target. As the pathogens have now been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to aim drugs at these toxic particles.”

Alzheimer’s disease leads to the death of nerve cells and tissue loss throughout the brain. Over time, the brain shrinks dramatically and the cell destruction causes memory failure, personality changes, and problems carrying out daily activities.

Scientists identified abnormal deposits called protein oligomers as the most likely suspects of the cause of dementia. Although proteins are normally responsible for important cell processes, when people have Alzheimer’s disease these proteins become rogue, form clumps and kill healthy nerve cells.

“A healthy brain has a quality control system that effectively disposes of potentially dangerous masses of proteins, known as aggregates,” said Vendruscolo. “As we age, the brain becomes less able to get rid of the dangerous deposits, leading to disease. It is like a household recycling system, if you have an efficient system in place then the clutter gets disposed of in a timely manner. If not, over time, you slowly but steadily accumulate junk that you don’t need. It is the same in the brain.”

The research was carried out by an international team of scientists that also included Professor Sir Christopher Dobson, Master of St John's College, University of Cambridge, at the Centre for Misfolding Diseases (CMD), which he co-founded. “This interdisciplinary study shows that it is possible not just to find compounds that target the toxic oligomers that give rise to neurodegenerative disorders but also to increase their potency in a rational manner,” he said. “It now makes it possible to design molecules that have specific effects on the various stages of disorders such as Alzheimer’s disease, and hopefully to convert them into drugs that can be used in a clinical environment.”

There have been approximately 400 clinical trials for Alzheimer’s disease but none of them has specifically targeted the pathogens that cause it. In the UK, dementia is the only condition in the top 10 causes of death without a treatment to prevent, cure or slow its progression.

“Our research is based on the major conceptual step of identifying protein oligomers as the pathogens and reports a method to systematically develop compounds to target them. This approach enables a new drug discovery strategy,” said Vendruscolo.

The team believes their first drug candidates could reach clinical trials in around two years. They have co-founded Wren Therapeutics, a biotechnology company based in the newly opened Chemistry of Health building, whose mission is to take the ideas developed at Cambridge and translate them into finding new ways to diagnose and treat Alzheimer’s disease and other misfolding disorders.

The group’s new strategy is based on a chemical kinetics approach developed in the last ten years by scientists led jointly by Professor Tuomas Knowles, also a Fellow at St John's College, Professor Dobson and Professor Vendruscolo, working at the new centre in Cambridge, in collaboration with scientists at Lund University led by Professor Sara Linse.

“Since the process of aggregation is highly dynamic, the framework of kinetics allows us to approach this problem in a new way and find approaches to stop the generation of toxic proteins species at their very source,” said Knowles.

“This is a detailed academic study looking at how quickly compounds are able to stop amyloid building up into toxic clumps, which are characteristic of Alzheimer’s disease,” said Dr David Reynolds, Chief Scientific Officer from Alzheimer’s Research UK. “With no treatments to slow or stop the diseases that cause dementia, it’s vital we improve approaches like this that could help refine the drug discovery progress and accelerate new treatments for people living with Alzheimer’s.”

Reference:
Sean Chia et al. ‘SAR by kinetics for drug discovery in protein misfolding diseases.’ PNAS (2018). DOI: 10.1073/pnas.1807884115

Adapted from a St John’s College press release.

Researchers from the University of Cambridge will shortly begin clinical trials of a new vaccine that builds on almost two decades of research to protect against diseases caused by RNA viruses. At the same time, they will begin studying the natural animal reservoirs of the viruses in an attempt to try and predict which strains are likely to cause future outbreaks, information that will be essential for creating effective vaccines.

Ebola, Lassa and Marburg viruses cause haemorrhagic fever, leading to severe disease, often with high mortality rates. Outbreaks can cause devastating local epidemics in the human population and to wildlife, including non-human primates. The recent Ebola epidemic in West Africa (2013–2016) killed over 11,000 people and devastated the infrastructure and economies of Liberia, Sierra Leone and Guinea.

A new approach to vaccine development

Professor Jonathan Heeney and colleagues at the Lab of Viral Zoonotics, University of Cambridge, have developed and successfully tested a trivalent vaccine in guinea pigs that protects against Ebola, Lassa and Marburg viruses. As a result, Professor Heeney has been awarded a further £2 million by Innovate UK and the Department of Health and Social Care to take the vaccine to clinical trials in humans.

The research takes a new approach pioneered by Professor Heeney and builds on Cambridge’s strengths in genomics, monoclonal antibody research and computational biology. It has led to the formation of DIOSynVax, a spin-out company of Cambridge Enterprise.

A virus’s genetic code is written into its RNA (just as ours is written into our DNA), which leads to the generation of proteins. When we are infected by a virus, our immune system responds to these proteins, known as ‘antigens’, producing antibodies that can identify and try to eliminate the invading pathogen.

The approach developed by Professor Heeney involves understanding how the immune system correctly identifies the virus from its proteins, and using this information to create ‘viruses’ that can generate an immune response. Using monoclonal antibodies – copies of antibodies taken from survivors of the target diseases – they can then test whether the body can effectively eliminate these fake viruses, leading to protection.

“We’ve taken fundamental science that stretches back almost two decades and developed a new approach to vaccine development,” says Professor Heeney. “This has the potential to dramatically reduce the time needed to produce new vaccines and change the way in which the industry makes them.”

With the new funding, the team hopes to scale up production while ensuring that the quality of the vaccine is maintained. They will then carry out toxicity tests in animals and human blood samples to test for potential adverse effects; if successful, they will then trial the vaccine in healthy human volunteers.

The funding is part of a £5m commitment from the Department of Health and Social Care to fund five projects to develop new vaccines with a ‘One Health’ focus, considering how the environment, the health of animals and the health of humans interact. This sits within the government’s £120m UK aid commitment to develop vaccines to help tackle diseases with epidemic potential.

Predicting the next outbreak

In recent Ebola outbreaks, the approach used successfully by the World Health Organization is known as ‘ring vaccination’, focused on vaccinating and monitoring a ring of people around each infected individual. However, this approach can only be used in response to an outbreak. In order for a vaccine to be used proactively – to prevent an outbreak in the first place – it is necessary to predict which strain or strains of a virus are most likely to cause future epidemics.

“A disproportionally high number of emerging and re-emerging diseases – from Ebola and Lassa through to rabies and influenza – are caused by RNA viruses carried naturally by animals,” says Professor Heeney. “We know very little about the viral diversity within these reservoir species and what enables them to spread to humans – and hence where the likely future threats lie.”

Viral genomes are notoriously variable due to the high mutation rates that occur during replication. These accumulate over time and result in evolution of the viruses as they circulate in their natural animal reservoir populations. If some viral variants arise and are able to adapt to use human cell receptors and are then able to escape immune defences, they may become highly infectious and cause large disease outbreaks.

“Vaccines are only as good as the antigen immune targets of the virus that they are designed for,” adds Professor Heeney. “If the antigen changes, the vaccine will no longer be effective. In most cases, current vaccine candidates against RNA viruses are from past human outbreaks with little or no information of future risks from viral variants carried in animal reservoirs, especially those with the potential for animal-to-human transmission.”

Professor Heeney has also received £1.4 million from the Biotechnology and Biological Sciences Research Council (BBSRC) to lead a project that aims to predict where future outbreaks may arise from and the likely strains, and to then use this knowledge to inform vaccine design. This One Health project enlists veterinarians, clinicians, ecologists and medical and public health workers in West Africa to understand how people catch Lassa fever from rat populations. Their work will include trapping rat species that carry these viruses and placing GPS tags to monitor their movements, as well as obtaining molecular, genomic and antibody data from the animals and viral sequences from infected rats.

Professor Melanie Welham, Executive Chair of BBSRC, says: “This important research from the team at the University of Cambridge is about providing effective treatments for some potentially deadly diseases spread by rats and bats: Lassa and Ebola respectively. Novel strategies to combat dangerous infections like these are essential and often underpin the development of much-needed next generation vaccines.

“Professor Heeney and team have already made a significant difference in this area, researching cross species transmissions of these viruses, with a view to developing vaccines for Ebola and Lassa that would be effective against multiple strains.”

In addition, the team is collaborating with Professor James Wood, Head of the Department of Veterinary Medicine at Cambridge, who is conducting a complementary study funded by the Global Challenges Research Fund to sample bat colonies in Ghana, believed to be a natural reservoir for the Ebola virus.

“Equipped with this information, we should be able to design better vaccine antigens for more effective and broadly-protective vaccines,” says Professor Heeney. “Combined with our accelerated vaccine development platform, this has the potential to have an enormous positive impact on global public health.”

A Vice-Chancellor’s job is always busy but, even by the usual standards of high office at a global university, the past academic year has been an eventful one for me at Cambridge. Over centuries, our university has demonstrated a remarkable ability to change with the times. At the moment, however, our resilience is being tested as the United Kingdom’s higher education sector is buffeted by gale force winds of change.

 Universities are coming to terms with the creation of new government bodies, including the Office for Students (OfS) and UK Research and Innovation (UKRI), which bring a new and expressly regulatory remit to their interaction with universities.

Political volatility is rife, which is perhaps to be expected in these anxious times. More troubling for someone who has long admired British higher education is the simmering sense of hostility towards universities. The two are not unrelated.

Discontent about universities most commonly plays out in the editorial pages of the national press, and in the not-so-far reaches of social media. It often takes the form of criticism of universities for being bastions of privilege. For not engaging with less-advantaged groups. For not encouraging more diversity. For not upholding free speech. For not being relevant. For not offering “value for money”.

Such grumblings are not a new thing. Almost thirty years ago, the University of Chicago sociologist Edward Shils noted that universities “are much criticised nowadays by government, civil servants, professors of education, journalists […] There are numerous reasons for these denunciations – some are good reasons, many are poor. Nevertheless […] societies cling to them. The universities do not survive simply because professors have a vested interest in their survival. That would never be enough. These societies cling to them because, in the last analysis, they are their last best hope for a transfigured existence.”

I stand with Shils in acknowledging that some criticism of universities is justified – as microcosms of society, universities can never be perfect institutions, and there is always more hard work to be done.

Some recent rebukes spring from the now fashionable suspicion of expertise, and the equally fashionable distrust in social institutions. New technologies have certainly fanned the flames of this distrust. Former U.S. President Barack Obama remarked that the abundance of information at our fingertips hasn’t made us more discerning of the truth, but only “more confident in our ignorance.”

Often, however, public disparagement of universities is the result of deeply entrenched misunderstandings about what universities do, and what they are for.

But perhaps, in responding to criticism, we might try to imagine what would happen if research-intensive universities like Cambridge simply did not exist. What would we be missing?

In what alternative settings might young people with career aspirations be able to make that crucial transition from the world of school to the world of work?

Where might those young men and women have the time or space to take on new ideas, to challenge them, and to develop their own?

Where might their potential for leadership – academic, entrepreneurial, political, civic – be freely incubated and honed?

What other institutions might be able to create, curate and communicate knowledge, unencumbered by the imperatives of profit or policy?

Who might our societies task with delivering the discoveries and innovations that will fuel our countries’ development?

Who else has the convening power to bring together governments, international organisations, businesses, the non-profit sector and leading researchers and thinkers to find common solutions to urgent global problems?

Critically: what other institutions might be able – or might even aspire – to do all of these things at once?

Of course I am biased, but I struggle to think of any.

Universities’ uniqueness as institutions does not give them the licence to divorce themselves from the expectations of the societies they serve. Indeed, the public trust placed in universities depends on universities’ ability to demonstrate that they take society’s goals and hopes seriously.

In a speech delivered in 1995, Gerhard Casper, then the President of Stanford University, also wondered what it would be like to live in a world without universities: “Let us remember that the world may need us, but it does not owe us anything,” he concluded. “Unless we make the case for our work in its entirety and pursue it rigorously and efficiently the world may tire of us and develop new approaches that it will consider adequate substitutes, even though… they may not be adequate in fact.”

When society does not feel we have its interests at heart, it is up to us to improve the ways we engage with it and communicate about what we do, how we do it and why.

For now, I take some comfort from early signs that the trend of loss of trust in experts and expertise, which calls dramatically into question the role of universities, may be reversing. A recent survey by Columbia University’s Teachers College concludes that most Americans (or at least most of the 3000 or so respondents) support government funding of higher education and recognise that, beyond graduates’ employability, there are significant benefits to the public from higher education.

The latest Edelman Trust Barometer, a yearly snapshot of global public trust in institutions, reveals that “voices of authority” – including technical and academic experts – are gaining ground, while the credibility of “a person like yourself” is waning significantly.

So the tide may be turning. I hope we are moving back to a place where the word “expert” is once again a badge of honour, rather than a term of abuse. But there is no cause for complacency. The moment is right for global universities to be confident in their missions, and also to speak up for knowledge, evidence and skills. We have a great story to tell – now is the time to tell it better.

This article was published in the Times Higher Educational Supplement.