This year’s Wolfson History Prize has been awarded to David Abulafia, Emeritus Professor of Mediterranean History and Fellow of Gonville and Caius College, for his book The Boundless Sea: A Human History of the Oceans, published last autumn.

The book traces the history of human movement, trade and communication around and across the world's greatest bodies of water, charting our relationship with the oceans from the time of the earliest seafaring societies to the maritime networks of today’s container ships.

The award was announced on Monday night at the Wolfson Prize’s first virtual ceremony, which featured guest appearances from previous winners, including Professor Mary Beard from the University’s Faculty of Classics. The virtual winner announcement can be viewed below.

The Chair of the Wolfson Prize judging panel, Professor David Cannadine, described the book as one of “deep scholarship” and said it was brilliantly written.

“The Boundless Sea tackles a world encompassing subject: humanity’s constantly changing relationship with the seas that cover most of our planet and on which our very lives depend,” Cannadine said.   

In The Boundless Sea, Abulafia follows merchants, explorers, pirates, cartographers and travellers in their quests for spices, gold, ivory, slaves, lands for settlement and knowledge of what lay beyond. It builds on Abulafia’s previous book The Great Sea, a human history of the Mediterranean.

The Boundless Sea aims to go beyond “Eurocentric” approaches, examining the Atlantic waters before Columbus, and showing how lucrative trade routes were created that carried goods and ideas along the "Silk Route of the Sea" well before Europeans burst into the Indian Ocean around 1500.

“Winning the Wolfson History Prize I see as a tribute to all of us who have been trying to communicate history to the public, writing in an accessible way without jargon, and making sure that people see the past as an essential part of our human experience,” said Abulafia, a former Chair of Cambridge’s Faculty of History.

The Wolfson History Prize is run and awarded by the Wolfson Foundation, an independent charity that awards grants in the fields of science, health, heritage, humanities, and the arts.  

Paul Ramsbottom, chief executive at the Wolfson Foundation, said that the Prize celebrates “the importance to society of outstanding and accessible history writing”.

“David Abulafia’s book is magnificently ambitious, brilliantly examining the changing, extraordinary connections between the vast oceans and humanity,” said Ramsbottom. “While broad in chronological sweep, this clearly has a strong contemporary resonance – as our relationship with the natural world (including the oceans) is under scrutiny as never before.”

Professor David Abulafia is a maritime historian who has spent his career teaching and researching in the History Faculty at Cambridge University. He is the Papathomas Professorial Fellow of Gonville and Caius College, and a Fellow of the British Academy.

The report, published today, quantifies the strong contribution the Babraham Research Campus makes to both the commercialisation of life science research and the life science knowledge base, enabling entrepreneur-driven businesses - including academic spin-outs - to form, and facilitating collaboration. It was commissioned by the Campus partners Babraham Bioscience Technologies (BBT) - the organisation which develops and manages the Babraham Research Campus, UKRI-BBSRC, and the Babraham Institute. 

The report’s key findings* include: 

• Company fundraising for those based on Campus is accelerated by an average of 5.1 months. 

• The market value of the top 14 companies on Campus is over £4 billion: an average 7.2 x return for investors. 

• 47% of funds raised in the Cambridge region were to those ventures located at the Babraham Research Campus. 

• The number of people employed on-site increased by over 90% from approximately 900 employees in 2011/12 to 1,700 employees in 2017/18. 

• Campus based companies are 20% larger by headcount than they otherwise would be if the Campus did not exist.

• The total gross value added (GVA) impact of the Campus on the UK economy is £285 million. 

In addition, over 75% of companies based on Campus who were surveyed as part of the research project considered their location on the Babraham Research Campus as either a very important or critically important factor in helping them access laboratory and office space on flexible and affordable terms. The ability to attract and retain talent was also highlighted as being greatly enhanced by being part of the Babraham Research Campus community.

“Investment in the Life Sciences Sector is clearly of fundamental importance to the growth of the UK economy and the well-being of its citizens," said Professor Pete Tyler at the University of Cambridge's Department of Land Economy, who led the report.

Derek Jones, CEO, BBT commented: “I am delighted to see that the findings from this report confirms our own internal data and anecdotal evidence of the impact of the Campus.  We have tried to ensure that the support we offer to life science companies, whether it be the provision of flexible lease structures; access to science capabilities; or the nurturing and engaging community, is impactful in terms of jobs, scientific progress and increased economic activity, both locally and for the UK as a whole. It appears in many respects that we have succeeded.  I would like to take this opportunity to thank all the BBT staff on Campus for the part they have played in making the Campus the success which from this evidence it is.”

Andy Richards, CBE, life science entrepreneur, investor and Chair of BBT added: “This impact report is based on a thorough quantitative and qualitative study. It provides an analysis that validates many of the hypotheses postulated as to why life-science companies in a concentrated and supportive ecosystem, such as that forged at the Babraham Research Campus within a vibrant cluster, have a differential advantage.  New ventures are able to start-up and develop rapidly with access to science, technology, talent and capital with fewer barriers allowing them to get into the all-important scale-up phase. It is good to see that those on the Campus value the initiatives that have been adopted and the special culture that has been created. As an investor it is a great place to nurture innovative start-ups and a fruitful place to have fast growing scale-ups. A truly low risk environment for ambitious impactful Bioscience.”

Dr Karen Lewis, Executive Director, UKRI- BBSRC said: “I am very pleased to see publication of this report, which highlights the significant contribution the Babraham Research Campus makes to the local and national research and innovation ecosystem.  UKRI-BBSRC is delighted that the report recognises the Campus as a dynamic place where institute researchers are able to deliver world leading bioscience, and life science companies can develop their science, build and scale-up their business, in a highly connected and collaborative community. The findings from this study highlight the vital role that long-term public and private investment has played in developing the Campus. The insights will help to ensure continued success in delivering economic growth and societal benefits.”

Professor Wolf Reik FRS, Acting Director, Babraham Institute said: "We are excited to see publication of this informative report, which highlights key impacts created by collaborations across the Babraham Research Campus. The Babraham Research Campus is unique in bringing together the world-leading academic research of the Babraham Institute and the vibrant and growing ecosystem of the Campus, with meaningful links existing at many different levels. These links are seen in collaborations, spin-out companies, joint funding, access to world class scientific facilities, training, and generally a better understanding of how fundamental science feeds into commercial developments with huge potential societal benefit."

Download a copy of the Executive Summary: ‘The Economic Impact of the Babraham Research Campus: An exploration of key findings’, access the full report and view the Babraham Research Campus Impact film. 

*Report data collated in 2019 covering the period 2011-2018.

Using social-contact data on more than 40,000 individuals from the BBC Pandemic database to simulate SARS-CoV-2 transmission in different settings and under different combinations of control measures, the researchers estimate that a high incidence of COVID-19 would require a considerable number of individuals to be quarantined to control infection. For example, a scenario in which 5,000 new symptomatic cases were diagnosed each day would likely require 150,000–200,000 contacts to be quarantined every day if no physical distancing was in place.

The study is the first time researchers have used social contact data to quantify the potential impact of control measures on reducing individual-level transmission of SARS-CoV-2 in specific settings. They aimed to identify not only what would theoretically control transmission, but what the practical implications of these measures would be in terms of numbers quarantined.

However, the authors note that the model is based on a series of assumptions about the effectiveness of testing, tracing, isolation, and quarantine—for example about the amount of time it takes to isolate cases with symptoms (average 2.6 days) and the likelihood that their contacts adhere to quarantine (90%)—which, although plausible, are optimistic.

“Our findings reinforce the growing body of evidence which suggests that we can’t rely on one single public health measure to achieve epidemic control,” said Dr Adam Kucharski from the London School of Hygiene & Tropical Medicine. “Successful strategies will likely include intensive testing and contact tracing supplemented with moderate forms of physical distancing, such as limiting the size of social gatherings and remote working, which can both reduce transmission and the number of contacts that need to be traced.”

He adds: “The huge scale of testing and contact tracing that is needed to reduce COVID-19 from spreading is resource intensive, and new app-based tracing, if adopted widely alongside traditional contact tracing, could enhance the effectiveness of identifying contacts, particularly those that would otherwise be missed.” 

In the study, researchers analysed data on how 40,162 people moved about the UK and interacted with others prior to COVID-19 to simulate how combinations of different testing, isolation, tracing, and physical distancing scenarios—such as app-based tracing, remote working, limits on different sized gatherings, and mass population-based testing—might contribute to reducing secondary cases [3]. They also modelled the rate at which the virus is transmitted—known as the reproductive number (R), or the average number of people each individual with the virus is likely to infect at a given moment—under different strategies. To keep the COVID-19 epidemic declining, R needs to be less than 1.

In the model, the secondary attack rate (the probability that a close contact of a confirmed case will be infected) was assumed to be 20% among household contacts and 6% among other contacts. The researchers calculated that, had no control measures been implemented, R would be 2.6—meaning that one infected person would infect, on average, 2–3 more people.

The model suggested that mass testing alone, with 5% of the population undergoing random testing each week (i.e. 460,000 tests per day in UK), would lower R to just 2.5, because so many infections would either be missed or detected too late (table 3 and infographic).

Compared with no control measures, self-isolation of symptomatic cases (at home) alone reduced transmission by an estimated 29% (lowering R to 1.8); whilst combining self-isolation, household quarantine, and tracing strategies could potentially lower transmission by as much as 47% (R 1.4) when using app-based contact tracing (assuming the app is adopted by 53% of the population), and by 64% with manual tracing of all contacts (R 0.94).

Achieving such a thorough level of contact tracing may be impractical, but the new study suggests that a large reduction in transmission could also be achieved by supplementing with moderate physical distancing measures. For example, they estimate that, limiting daily contacts outside home, school, and work to four people (e.g. by restricting mass gatherings) along with manual tracing of acquaintances only (i.e. people they have met before) and app-based tracing, would have the greatest impact, reducing disease spread by 66%, and lowering R to 0.87. However, they note that the effectiveness of manual contact tracing strategies is highly dependent on how many contacts are successfully traced, with a high level of tracing required to ensure R is lower than 1, especially if it takes time to isolate symptomatic cases.

The researchers also modelled the number of contacts that might need to be quarantined under different contact tracing strategies. They estimate that a scenario in which 1,000 new symptomatic cases were reported daily would likely require a minimum of 15,000 contacts quarantined every day (isolation plus app-based testing) and a maximum of 41,000 (isolation plus manual tracing all contacts). This could increase to an average of 150,000–200,000 contacts quarantined daily in a scenario where 5,000 new symptomatic cases were diagnosed each day (table 4).

“Our results highlight several characteristics of SARS-CoV-2 which make effective isolation and contact tracing challenging. The high rate of transmission, the short time between one person becoming infected and infecting another, and transmission that occurs without symptoms all make things difficult,” said co-author Dr Hannah Fry from University College London. “If there are a lot of symptomatic COVID-19 cases, then tracing, testing, and trying to quarantine a huge number of contacts will be a big challenge. How well we manage it will affect how and when it is possible to reduce transmission predominantly through targeted isolation and tracing measures or whether ongoing physical distancing measures will be required to control the epidemic.”

According to co-author Professor Julia Gog from Cambridge’s Department of Applied Mathematics and Theoretical Physics, “Planning for control based on isolation and contact tracing should consider the likely need for large numbers of cases to be tested and also a large number of contacts rapidly quarantined. Crucially, this work is able to quantify the scales of what is needed for a successful control strategy involving tracing and isolation by making use of the dataset from the BBC pandemic project. The BBC data gives a uniquely detailed picture of how people in the UK mix and the extent of contact tracing that will be necessary if we return to social mixing patterns as they were before the pandemic.”

The authors highlight several limitations to their study, including that it did not consider more detailed settings beyond home, school, work, or ‘other’ categories, or explicitly include imported infections, which may be detected at a different rate to local infections.

Writing in a linked Comment, Professor Raina MacIntyre (who was not involved in the study) from The University of New South Wales, Australia, says, “Whilst the study is specific to the UK, the findings are relevant to all countries. For countries which are opening up for business and resuming social activities, as social contacts increase, non-pharmaceutical interventions become even more critical. It may even be worthwhile for countries to invest in strategies to vastly improve the uptake of contact tracing apps to enable rapid response to resurgence of COVID-19. If you don’t trace, you leave a chain of transmission free to grow undetected and exponentially. With 80% of cases being mild, it may take several generations of silent epidemic growth before it is even recognised.”

Reference:
Adam J Kucharski et al. 'Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study.' The Lancet Infectious Diseases (2020). DOI: 10.1016/ S1473-3099(20)30457-6

Adapted from a press release by The Lancet.

Populations in England’s poorest towns have on average 12 fewer years of good health than those in the country’s richest towns, according to new research from the University of Cambridge’s Bennett Institute.

The study shows that the number of hospital admissions for self-harm in the most deprived towns is – on average – almost double that of the most affluent, with alcohol-related admissions over 75% higher than in the least deprived towns.  

Lung cancer is twice as prevalent in the most deprived towns, and child obesity in the poorest towns stands at an average of 23% by the end of primary school, compared to around 12% in the wealthiest. 

In fact, researchers say the overall life expectancy of town-based populations is “moving in a worse direction” compared to cities – with female life expectancy now higher in English cities than towns for the first time this century.

“The previous pattern of rising life expectancy has stalled or gone into reverse in many English towns,” said Prof Mike Kenny, report coauthor and Director of the Bennett Institute for Public Policy. “Declining fortunes and debates over Brexit have highlighted the chasm that divides many town inhabitants from those in cities.

“However, on some key health measures, inequalities between towns are much greater than the average difference between towns and cities. People in England’s most deprived towns lose over a decade of good health compared to the populations of wealthy towns.”

“There is an overriding need for policies to address the large and widening gaps in the health and opportunities of many towns. These policies should be integral to post-pandemic economic recovery agendas,” Kenny said.

The team found a “strong geographical context”: most of the healthiest towns are in the South East, while most of the unhealthiest towns are situated in former industrial areas of Northern England.

Towns with the longest life expectancy include Frimley in Surrey and Filton, near Bristol. Populations with the shortest lives, on average, were found in Thurnscoe, near Barnsley, and Oldham.

Two seaside towns at either end of the country, Blackpool in the Northwest and Jaywick in East Anglia, had the highest levels of self-harm. Another coastal town, Newbiggin-by-the-sea, near the former collieries north of Newcastle, had the highest child obesity rates. Eccles and Salford on the outskirts of Manchester are the towns with most alcohol-related hospital admissions.

Hertforshire contains a number of England’s healthiest and wealthiest towns, such as Radlett and Harpenden, while many of the country’s unhealthiest towns – scattered across the north – are also those with the largest populations.

The provision of public green spaces – so important for physical and mental health, and never more so than during the recent coronavirus lockdown – was another dividing line between wealthy and unhealthy towns.

The most affluent towns are on average twice as likely as the most deprived towns to have a common or municipal park within their “built-up area boundary”, according to researchers.

They also found that the most deprived towns had – on average, per capita – 50% more fast food shops than the most affluent towns.

“More deprived towns are much less likely to have a green town centre and much more likely to have high numbers of fast food outlets than their wealthier counterparts,” said Ben Goodair, the report’s lead researcher. “Both these factors contribute significantly to the widening of geographic health inequalities in England.”

“There is every chance that the coronavirus pandemic will make the inequalities we see in our research even worse,” said Goodair. “Many deprived towns have an older age profile, and are more susceptible to the worst effects of the virus, as well as low employment prospects that will be reduced even further by the economic consequences of lockdown.” 

The report only looked at COVID-19 data up to mid-April, but found a slightly higher death rate was already visible in the more deprived towns during the early phase of the pandemic.

Added Kenny: “The current government has said it is committed to ‘levelling up’ England’s regions. Tackling the factors damaging the health of the poorest towns will have to go much further than the hospital walls, including boosting skill levels, promoting local employment and building community resilience.” 

In the coming years, this method and others based on this approach could lead to tests that more accurately determine if a patient is likely to relapse after treatment and could pave the way for the development of pinprick home blood tests to monitor patients. The research, funded by Cancer Research UK, is published in the journal Science Translational Medicine

The technique uses personalised genetic testing of a patient’s tumour to search blood samples for hundreds of different genetic mutations in circulating tumour DNA (ctDNA); DNA released by cancer cells into the bloodstream.

Combined with new methods to analyse this data to remove background noise and enhance the signal, the team was able to reach a level of sensitivity that in some cases could find one mutant DNA molecule among a million pieces of DNA – approximately ten times more sensitive than previous methods.

Dr Nitzan Rosenfeld, senior group leader at the Cancer Research UK Cambridge Institute who led the team that conducted this research, said: “Personalised tests that can detect if cancer is still present, or find it early if it is returning, are now being tested in clinical trials.

While this may be several years away from clinical use, our research shows what is possible when we push such approaches to an extreme. It demonstrates that the levels of sensitivity we’ve come to accept in recent years in relation to testing for ctDNA can be dramatically improved. At present this is still experimental, but technology is advancing rapidly, and in the near future tests with such sensitivity could make a real difference to patients.”

Detecting ctDNA in blood samples is what is known as a ‘liquid biopsy’. It allows doctors to find out more about a patient’s cancer without the need for invasive surgery. The technique is important for monitoring cancer patients, particularly after they’ve received treatment, as it can be an indicator of whether the treatment was successful and if the patient might relapse. In some situations, other types of tests can be used to detect some cancers before they display any symptoms or show up on a scan.

Currently, the sensitivity of the methods depends on having a high enough number of mutant pieces of DNA, either relative to background DNA or in absolute numbers. When the amount of ctDNA is low, a test can produce a negative result even if a patient has residual cancer in their body that could lead to relapse.

A single tumour will contain many different mutations that caused the cancer to form. While some of them are commonly known across certain cancer types, such as EGFR in lung cancer, the overall set of mutations for a tumour varies from person to person. By analysing the genetic makeup of an individual’s tumour and targeting a set of mutations in a personalised way, liquid biopsies to monitor cancer can become much more sensitive.

Until recently, these personalised liquid biopsies have searched for around 10-20 mutations in the blood and up to around 100 at most. In the material from a tube of blood, these would be able to detect ctDNA to levels on the range of one mutant molecule among 30,000 pieces of DNA.

This new technique looks for hundreds and sometimes thousands of mutations in each blood sample, routinely achieving a sensitivity of one mutant molecule per 100,000, and under optimal conditions can reach a level measured in parts per million.

The researchers describe traditional liquid biopsies as like looking for a needle in a haystack. This new approach of using personalised genetic profiles to search for many different mutations rather than just one, increases the number of ‘needles’ that can be found, making chances of success more likely.

They also say the ‘haystack’ itself could be made smaller; as the methods developed for this research could mean that smaller and smaller amounts of blood could be required for the test to still work. Eventually, this could lead to tests that would require only a pinprick of blood – a procedure that patients could perform at home – that would then be sent to a lab for analysis. This would not only mean fewer visits to the hospital, but would also allow the patient to be more frequently monitored.

The researchers and their collaborators studied samples from 105 cancer patients, testing the method on small sets of patients with five different cancer types, with both early and late stage disease.

The method showed promising results and was able to detect ctDNA at high sensitivity in patients with advanced breast and melanoma cancer, and in patients with glioblastoma, which is notoriously difficult to detect in blood. The test was also able to detect ctDNA in patients with earlier-stage disease, where the level of ctDNA in the blood is much lower and difficult to find. This included patients with lung or breast cancer, as well as patients with early-stage melanoma who had already had surgery, which makes detection even more difficult.

In ongoing studies funded by Cancer Research UK, the team and their collaborators plan to use this method to measure ctDNA levels in individuals who are at high risk of developing cancer to help refine future tests for cancer early detection.

Michelle Mitchell, chief executive of Cancer Research UK, said: “Liquid biopsies have the potential to revolutionise all aspects of cancer care, from early detection to personalised treatment and monitoring. As a field that relies heavily on technology, this kind of proof-of-concept research is incredibly important for us to invest in as a charity, as it’s what makes potential future leaps in the use of liquid biopsies possible, and ultimately save more lives.”

Reference:
Jonathan C. M. Wan et al. ‘ctDNA monitoring using patient-specific sequencing and integration of variant reads.’ Science Translational Medicine (2020). DOI: 10.1126/scitranslmed.aaz8084

Adapted from a Cancer Research UK press release.

The report, by researchers at the University of Cambridge, Edge Hill University and the UK-based charity Stand Alone, brings together over 800 responses to a survey sent out to the charity’s UK community. The survey asked individuals about the experience of being estranged from family during the current crisis, and how it has impacted them and their family relationships. Over half of the respondents said they felt more isolated now than they had before lockdown.

During the pandemic many estranged people have become more conscious of not having family to support them, for example to help with grocery shopping while they can’t go to the supermarket themselves. For some it has brought the realisation that their well-being is not important to other family members, and compounded the feeling of being unloved and uncared for. 

78% of respondents had maintained the same level of non-contact with their estranged family member during lockdown, and 6% had experienced even less contact. One respondent said they hadn’t spoken to another person for over two months. 

“There’s a lot of stigma around estrangement, and people in this situation have experienced it in a heightened way during lockdown. Many have become more aware that they have smaller support networks than others,” said Dr Susan Imrie at the University of Cambridge’s Centre for Family Research, who was involved in the study.

The researchers say the importance of family relationships has been highlighted repeatedly throughout lockdown in television advertising, news headlines and social media. But for those who were already estranged from family, the pandemic and the messages surrounding it have compounded feelings of stigma and social isolation.

“Since lockdown began there has been a lot of talk about what family members should be doing to support each other at this time of crisis. We’ve all been encouraged to keep in touch with relatives through Skype and FaceTime. But this has really compounded feelings of isolation for those who don’t have close family relationships,” said Dr Sarah Foley at the University of Cambridge’s Centre for Family Research, who was also involved in the study.

It is estimated that over five million people in the UK are estranged from a family member, but despite being so common it is not something that is widely known about or discussed. 

“Despite the assumption that family members will be a source of support during the COVID-19 crisis, this is not always the case. One in five families across the UK have no contact with an estranged family member, and this new report finds that very little has changed for them during the pandemic,” said Dr Becca Bland, CEO of Stand Alone.

Stand Alone supports people who have more challenging experiences of family, and who are estranged from their entire family or a key family member. The reasons behind estrangement in the community are varied: some are surviving abuse and neglect, others have been distanced for coming out as LGBT+ or for rejecting cultural, religious and political values. It is the only charity in the UK that works to support people who are estranged from family members.

The results of this study will help Stand Alone understand how best to target support during the pandemic. The researchers also hope it will raise awareness of family estrangement so that it can be handled more sensitively as lockdown continues.

The researchers say it is difficult to know the extent to which the survey respondents reflect the level of estrangement from family across the UK population as a whole.

A minority of the survey respondents who were estranged from family said they actually felt more connected during lockdown because everyone else was suddenly unable to see their family too. They hoped this might help others understand their situation better.

“Different people are being affected differently by the lockdown. Advice about coping shouldn’t assume that everyone has family relationships that are close and loving. Even subtle changes in the language used could have a really positive effect on people’s experiences,” said Dr Lucy Blake, Senior Lecturer in Children, Young People and Families at Edge Hill University, who was also involved in the study.

Reference
Family Estrangement and the COVID-19 Crisis: A closer look at how broken family relationships have been impacted by the COVID-19 crisis. Report by Dr Lucy Blake (Edge Hill University), Dr Becca Bland (Stand Alone), Dr Sarah Foley and Dr Susan Imrie (Centre for Family Research, University of Cambridge).

I work at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) in the Department of Medicine. We have stayed operational throughout the COVID-19 pandemic. I was impressed by the way CITIID came together, speeding up completion of our containment level 3 labs (designed to safely handle infectious diseases) by four to six months. This institute came alive at the time it was needed most, and our work spans basic science to diagnostics. Few places in the world have been able to do this. 

I’m used to working with another killer disease that creates a lot of fear. I’m a virologist, and I’ve spent the last decade studying HIV. The work I’ve done has been useful preparation for the COVID-19 pandemic, so it felt like the team was in the right place at the right time. Both HIV and COVID-19 are multi-system diseases, and HIV is still enigmatic after 30 years. As we discover the effects of COVID-19 on the human body, such as patients developing heart problems and lung damage, it looks like it will have far-reaching implications that will take a long time to sort out. 

We wanted to use our expertise as virologists to help tackle COVID-19. We made ‘pseudo-viruses’ that are part coronavirus and part HIV, but are very safe and don’t cause disease, to try and understand how antibodies were working in people infected with the virus. By taking blood samples from COVID-19 patients and mixing them with our pseudo-virus, we could see that these patients had immunity that would prevent our virus infecting their cells.

One of the big problems with COVID-19 has been making a diagnosis quickly. Tests are being sent off to a lab and taking two to four days to come back, and that’s not quick enough. We’ve been trialling a new rapid point-of-care test to look for antibodies in patients - and we needed the corresponding lab-based study to understand how well this was working. We’re now about to implement a point-of-care antibody test to help diagnosis.

We’ve also recently introduced a new rapid diagnostic test called SAMBA II at Addenbrooke’s Hospital. This followed a four week clinical study we did in April that showed using this test was quick and effective, and that it had a very significant impact on preserving hospital capacity and patient safety. The SAMBA II machines were developed by a University of Cambridge spinout company called Diagnostics for the Real World. You take the nose or throat swab for people who you think have COVID-19, and get a result back in 90-minutes. 

The lab has also started a programme to understand the basis of the second, inflammation-mediated part of the disease. This is likely to involve macrophages - the white blood cells that locate disease particles in the body and engulf them. We’re trying to understand the effects of low oxygen levels on the way macrophages behave, and find out why some patients get so much inflammation in their lungs that it becomes fatal. We’re also looking at whether drugs such as azithromyin and chloroquine can stop the inflammation - so not working directly on the virus, but trying to stop the body reacting against itself.

I think there are three big challenges posed by the pandemic: developing wide-scale rapid tests to keep track of the virus and control outbreaks, designing a vaccine that works throughout time and over long periods, and finding effective treatments. The virus is probably going to be circulating for some years, but it may mutate. So even if we have a vaccine we need to make sure it carries on working. We also need really good treatments in order to test vaccines. For a lot of diseases we can give someone a vaccine, and then infect them with the disease to see whether the vaccine works. But while we don’t have any good treatments for COVID-19, we can’t do that.

This has been a big team effort involving lots of people. We’re collaborating with the MRC Laboratory for Molecular Biology, and with colleagues in the Department of Pathology. There are also many people who switched the focus of their research to join us - some were interested in viruses, some were immunologists, but most were not coronavirus experts. Before COVID-19 there were very few of those.

The pandemic has shown us that we can make huge strides in understanding things very quickly and then deal with them appropriately, when we try. We need to communicate well, prepare early, and work together for a common goal. I hope we can all learn from this experience. The experience of the interaction between scientists and government is also something we can learn from.

In the future I want to keep doing COVID-19 research alongside the HIV research. This is partly because there’ll be plenty to do, and partly because I think there’s lots to learn that could translate to other viruses. The next pandemic may be a related virus, so we really do need to keep plugging away.
 
When the pandemic is over I’m looking forward to travelling again, for work and pleasure. I have projects in South Africa and I want to be back there to get them restarted. That’s where I see the need for our work on both HIV and COVID-19.
 
Ravi Gupta has been Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases since 2019. Deployment of the SAMBA II rapid diagnostic testing machines in Addenbrooke's Hospital was reported here, and in a BBC interview, in April 2020.

How you can support Cambridge’s COVID-19 research

Supported by a donation from Schmidt Futures, a philanthropic initiative founded by Eric and Wendy Schmidt, the Accelerate Programme for Scientific Discovery will level the playing field for young researchers, providing them with specialised training in these powerful techniques, which have the potential to speed up the pace of discovery across a range of disciplines.

The programme will initially be aimed at researchers in STEMM (science, technology, engineering, mathematics and medicine), but will grow to include arts, humanities and social science researchers who want to use machine learning skills to accelerate their research.

The Accelerate Programme will be led by Professor Neil Lawrence, DeepMind Professor of Machine Learning.

“Machine learning and AI are increasingly part of our day-to-day lives, but they aren’t being used as effectively as they could be, due in part to major gaps of understanding between different research disciplines,” said Lawrence. “This programme will help us to close these gaps by training physicists, biologists, chemists and other scientists in the latest machine learning techniques, giving them the skills they need while accelerating the excellent research already taking place at the University.”

“As the intellectual home of Alan Turing, the father of artificial intelligence and modern computer science, Cambridge has long fostered technological innovation and invention,” said Vice-Chancellor Professor Stephen Toope. “This programme will help ensure that Cambridge continues to be a beacon for the very best young global researchers, and that we’re giving them the tools they need to thrive.”

The five-year programme will be designed and delivered by four new early-career specialists, who will work with researchers from the Department of Computer Science and Technology as well as collaborators from industry. In the first year, the specialists will provide structured training in machine learning techniques to 32 PhD students and postdoctoral researchers, with training provided to a total of 160 PhD students and postdocs over the first five years of the programme. The specialists will also have the opportunity to pursue their own research interests as part of their fellowships.

The programme will also benefit from in-kind support from DeepMind. The world-leading British AI company, founded by Queens’ College alumnus Demis Hassabis, has assisted in the development of the programme, and will offer programme participants guest lectures from DeepMind's research team and the opportunity to apply for internship positions.

“Machine learning and AI have the potential to revolutionise any number of fields, but there simply aren’t enough scientists with machine learning skills in those fields at the moment,” said Professor Ann Copestake, Head of the Department of Computer Science and Technology. “This programme will combine Cambridge’s research depth and breadth with the unparalleled expertise in machine learning research we have here in the Department, to build a new type of research culture equipped to face the challenges and opportunities of the 21^st century.”

“We are delighted to support this far-reaching program at Cambridge,” said Stuart Feldman, Chief Scientist at Schmidt Futures. “We expect it to accelerate the use of new techniques across the broad range of research as well as enhance the AI knowledge of a large number of early-stage researchers at this superb university.”

One of the goals of the Accelerate Programme is to build a network of machine learning experts across the University. The PhD students and postdoctoral researchers who are trained through the Programme will share their knowledge with colleagues, building up capacity throughout Cambridge at scale.

Cambridge’s AI expertise has recently been expanded with the appointment of Dr Ferenc Huszár, who joins the University from Twitter, Dr Carl Henrik Ek, who is joining from the University of Bristol, and Dr Nicholas Lane who is joining from the University of Oxford.

The results, published today in the journal Molecular Psychiatry, describe how a chemical messenger in the brain called dopamine ‘tunes’ the brain to the level of novelty in a situation, and helps us to respond appropriately - by either updating our model of reality or discarding the information as unimportant. 

The researchers found that a brain region called the superior frontal cortex is important for signaling the correct degree of learning required, depending on the novelty of a situation. Patients with psychosis have faulty brain activation in this region during learning, which could lead them to believe things that are not real.

“Novelty and uncertainty signals in the brain are very important for learning and forming beliefs. When these signals are faulty, they can lead people to form mistaken beliefs, which in time can become delusions,” said Dr Graham Murray from the University of Cambridge’s Department of Psychiatry, who jointly led the research.

In novel situations, our brain compares what we know with the new information it receives, and the difference between these is called the ‘prediction error’. The brain updates beliefs according to the size of this prediction error: large errors signal that the brain’s model of the world is inaccurate, thereby increasing the amount that is learned from new information.

Psychosis is a condition where people have difficulty distinguishing between what is real and what is not. It involves abnormalities in a brain chemical messenger called dopamine, but how this relates to patient experiences of delusions and hallucinations has until now remained a mystery. 

The new study involved 20 patients who were already unwell with psychosis, 24 patients with milder symptoms that put them at risk of the condition, and 89 healthy volunteers. 

Participants were put into a brain scanning machine called a functional MRI and asked to play a computer game. This allowed the researchers to record activity in the participants’ brains as they engaged in situations with a potential variety of outcomes.

In a second part of the study, 59 of the healthy volunteers had their brains scanned after taking medications that act on the signaling of dopamine in the brain. These medications changed the way that the superior frontal cortex prediction error responses were tuned to the degree of uncertainty.

“Normally, the activity of the superior frontal cortex is finely tuned to signal the level of uncertainty during learning. But by altering dopamine signaling with medication, we can change the reactivity of this region. When we integrate this finding with the results from patients with psychosis, it points to new treatment development pathways,” said Dr Kelly Diederen from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, who jointly led the study with Dr Murray.

In addition to studying brain activation, the researchers developed mathematical models of the choices made by participants in the computer game, to better understand the strategies of how people learn. They found that patients with psychosis did not take into account the level of uncertainty during learning, which may be a good strategy in some circumstances but could lead to problems in others.  Learning problems were related to alterations in brain activation in the superior frontal cortex, with patients with severe symptoms of psychosis showing more significant alterations. 

“While these kind of abnormal brain responses were predicted several years ago, this is the first time the changes have actually been shown to be present. The results give us confidence that our theoretical models of psychosis are correct,” said Dr Joost Haarsma from University College London, first author of the study.

This research was funded by the Wellcome Trust. 

Reference
Haarsma, J. et al: ‘Precision-weighting of cortical unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis.’ Molecular Psychiatry, June 2020. DOI: 10.1038/s41380-020-0803-8

A research programme pioneering the use of whole genome sequencing in the NHS has diagnosed hundreds of patients and discovered new genetic causes of disease. Whole genome sequencing is the technology used by the 100,000 Genomes Project, a service set up by the government to introduce routine genetic diagnostic testing in the NHS.

The results of the study, published in the journal Nature, demonstrate that sequencing the whole genomes of large numbers of individuals in a standardised way can improve the diagnosis and treatment of patients with rare diseases. It was led by researchers at the University of Cambridge together with Genomics England.

The researchers studied the genomes of groups of patients with similar symptoms, affecting different tissues, such as the brain, eyes, blood or the immune system. They identified a genetic diagnosis for 60% of individuals in one group of patients with early loss of vision.

The programme offered whole-genome sequencing as a diagnostic test to patients with rare diseases across an integrated health system, a world first in clinical genomics. The integration of genetic research with NHS diagnostic systems increases the likelihood that a patient will receive a diagnosis and the chance that a diagnosis will be provided within weeks rather than months.

“Around 40,000 children are born each year with a rare inherited disease in the UK alone. Sadly, it takes more than two years, on average, for them to be diagnosed,” said Willem Ouwehand, Professor of Experimental Haematology at Cambridge, the National Institute for Health Research BioResource and NHS Blood and Transplant Principal Investigator. “We felt it was vital to shorten this odyssey for patients and parents.

“This research shows that quicker and better genetic diagnosis will be possible for more NHS patients.”

In the study, funded principally by the National Institute for Health Research, the entire genomes of almost 10,000 NHS patients with rare diseases were sequenced and searched for genetic causes of their conditions. Previously unobserved genetic differences causing known rare diseases were identified, in addition to genetic differences causing completely new genetic diseases.

The team identified more than 172 million genetic differences in the genomes of the patients, many of which were previously unknown. Most of these genetic differences have no effect on human health, so the researchers used new statistical methods and powerful supercomputers to search for the differences which cause disease – a few hundred ‘needles in the haystack’.

“Our study demonstrates the value of whole-genome sequencing in this context and provides a suite of new diagnostic tools, some of which have already led to improved patient care,” said Professor Adrian Thrasher of the UCL Great Ormond Street Institute of Child Health (ICH) in London.

Using a new analysis method developed specifically for the project, the team identified 95 genes in which rare genetic differences are statistically very likely to be the cause of rare diseases. Genetic differences in at least 79 of these genes have been shown definitively to cause disease.

The team searched for rare genetic differences in almost all of the 3.2 billion DNA letters that make up the genome of each patient. This contrasts with current clinical genomics tests, which usually examine a small fraction of the letters, where genetic differences are thought most likely to cause disease. By searching the entire genome researchers were able to explore the ‘switches and dimmers’ of the genome – the regulatory elements in DNA that control the activity of the thousands of genes.

The team showed that rare differences in these switches and dimmers, rather than disrupting the gene itself, affect whether or not the gene can be switched on at the correct intensity. Identifying genetic changes in regulatory elements that cause rare disease is not possible with the clinical genomics tests currently used by health services worldwide. It is only possible if the whole of the genetic code is analysed for each patient.

“We have shown that sequencing the whole genomes of patients with rare diseases routinely within a health system provides a more rapid and sensitive diagnostic service to patients than the previous fragmentary approach, and, simultaneously, it enhances genetics research for the future benefit of patients still waiting for a diagnosis,” said Dr Ernest Turro from the University of Cambridge and the NIHR BioResource.

“Thanks to the contributions of hundreds of physicians and researchers across the UK and abroad, we were able to study patients in sufficient numbers to identify the causes of even very rare diseases.”

Although individual rare diseases affect a very small proportion of the population, there exist thousands of rare diseases and, together, they affect more than three million people in the UK. To tackle this challenge, the NIHR BioResource created a network of 57 NHS hospitals which focus on the care of patients with rare diseases. Nearly 1000 doctors and nurses working at these hospitals made the project possible by asking their patients and, in some cases, the parents of affected children to join the NIHR BioResource.

“In setting up the NIHR BioResource Project, we were taking uncharted steps in a determined effort to improve diagnosis and treatment for patients in the NHS and further afield” said Dr Louise Wood, Director of Science, Research and Evidence at the Department of Health and Social Care.“This research has demonstrated that patients, their families and the health service can all benefit from placing genomic sequencing at the forefront of clinical care in appropriate settings.

Based on the emerging data from the present NIHR BioResource study and other studies by Genomics England, the UK government announced in October 2018 that the NHS will offer whole-genome sequencing analysis for all seriously ill children with a suspected genetic disorder, including those with cancer. The sequencing of whole genomes will expand to one million genomes per year by 2024.

Whole-genome sequencing will be phased in nationally for the diagnosis of rare diseases as the ‘standard of care’, ensuring equivalent care across the country.

The benefits include a faster diagnosis for patients, reduced costs for health services, improved understanding of the reasons they suffer from disease for patients and their carers and improved provision of treatment.

Reference:
Turro E et al. ‘Whole-genome sequencing of patients with rare diseases in a national health system.’ Nature (2020). DOI: 10.1038/s41586-020-2434-2

Adapted from an NIHR press release.

I’ve spent most of the last few years in Kenya and eastern Africa. When I wasn’t there, I was usually scampering back and forth between the Alison Richard Building on Cambridge’s Sidgwick site and King’s College, somehow covering my daily steps quota. Now I’m working at the kitchen table, my son’s desk in his room, or the bedroom. I’m missing the study we never had!

I work on the ‘Risk Communications and Community Engagement’ part of the global pandemic response. This is about understanding the experience of the virus from a community perspective, then delivering trusted and effective messaging to support healthy behaviours as well as communicating feedback to public health actors and authorities.

My own expertise lies in understanding citizen-authority relations in developing countries, and how citizens engage with and hold to account decision-makers in policy-making and service delivery. Over the years I’ve also worked on innovations using media and communication technology to engage with and hear from hard-to-reach populations, and derive rapid social insights from large volumes of local language textual data. My work led to the spin-off Africa’s Voices Foundation, a non-profit I cofounded, based in Kenya. The team deploys our novel method combining local language radio and a free SMS channel to deliver governance and social change programmes.  

As soon as COVID-19 hit, we were engaging populations in Kenya and Somalia. Two years ago, I was supported by the Wellcome Trust and UK DFID to evaluate the use of our interactive radio method for rapid social insights in health crises, as part of a global rethink following the West African Ebola outbreak. We’re now using this method and delivering insights to the wider national and international COVID-19 response.

I also work on improving socio-technical solutions for effective risk communication and community engagement, in collaboration with Luke Church in the Computer Laboratory. COVID-19 motivated us to rapidly build a communications tool for handling large volumes of one-to-one SMS conversations. If people raise urgent concerns, convey rumours, misinformation or stigma, or ask questions about COVID-19, the Africa’s Voices team needs to respond to each person quickly and empathetically but using an approved response protocol. A bot simply won’t do. We developed a tool called katikati that’s being used in Somalia right now, handling many thousands of interactions each week.   

Trust is the biggest challenge of this pandemic. Who and what is trusted by people determines how they respond. How much do we trust in ourselves and our communities, in our social/religious leaders, in scientific expertise, and in people, nations, governments and international agencies globally? Without trust playing a very large role, we don’t flatten the curve through distancing and hygiene, achieve track and trace, protect the vulnerable, adopt new vaccines, reopen our businesses, institutions, even our borders, and ready ourselves to tackle a possible second wave. 

Our research is about unearthing the worldviews and perspectives of communities, then thinking about the communications that will make sense for them. Imagine you’re a Somali forcibly displaced from your home due to drought and conflict, now in a crowded informal camp with no running water and limited sanitation, in the midst of a locust plague that is wreaking havoc on food production and livelihoods. Your life is precarious already, and you face a range of risks and anxieties. You are told by a government announcement that this new virus is sweeping the world, and to protect your community you must change the way you live in ways that are hard to achieve and put your livelihood in greater peril. You turn to your local Sheikh for guidance, as you always do - it’s what they say that matters, not what the government, or WHO, or UNICEF is saying.    

Somehow this pandemic arrived when our communication technologies and data transmission capabilities were ready for global remote networked collaboration. We might all be a bit ‘Zoomed out’, but I’m amazed every day by how I can collaborate on a response in Somalia with multiple organisations and far flung individuals. Ten years ago cloud computing was in its infancy, and we could not have managed this.

I am more motivated and passionate than ever about the importance and value of applied interdisciplinary research that really harnesses expertise across social, biomedical and technological sciences. In Cambridge there’s a strong spirit of collaboration across departments and disciplines that’s very inspiring. I’ve seen this through the support given to me by initiatives such as Cambridge-Africa and Cambridge Global Challenges.

When the pandemic is over I’m looking forward to traveling back to Kenya and eastern Africa and meeting up again with the amazing Africa’s Voices team.

Sharath Srinivasan is David and Elaine Potter Lecturer in Governance & Human Rights and Co-Director of the Centre of Governance and Human Rights (CGHR), and Fellow of King's College, Cambridge. Read more about the Africa's Voices project on Somali views in the early days of COVID-19.

How you can support Cambridge’s COVID-19 research

The authors of the new report argue that well-meaning but simplistic actions such as complete bans on hunting and wildlife trade, ‘wet markets’ or consumption of wild animals may be unachievable and are not enough to prevent another pandemic. Measures like these can be difficult to implement so must be carefully planned to prevent proliferation of illegal trade, or alienation and increasing hardship for local communities across the world who depend on wild animals as food.

Zoonotic diseases of epidemic potential can also transmit from farmed wildlife (such as civets) and domesticated animals (as exemplified by swine flu and avian flu), with greater risks occurring where humans, livestock and wildlife closely interact. 

Compiled by a team of 25 international experts, the study considered all major ways that diseases with high potential for human to human transmission can jump from animals to humans (termed zoonotic diseases). The authors say that dealing with such a complicated mix of potential sources of infection requires widespread changes to the ways humans and animals interact.

“A lot of recent campaigns have focused on banning the trade of wild animals, and dealing with wild animal trade is really important yet it’s only one of many potential routes of infection. We should not assume the next pandemic will arise in the same way as COVID-19; we need to be acting on a wider scale to reduce the risk,” said Professor William Sutherland in the University of Cambridge’s Department of Zoology and the BioRISC Research Initiative at St Catharine’s College, Cambridge, who headed the research.

Potential ways another human pandemic could arise include: wildlife farming, transport, trade and consumption; international or long distance trade of livestock; international trade of exotic animals for pets; increased human encroachment into wildlife habitats; antimicrobial resistance - especially in relation to intensive farming and pollution; and bioterrorism.

Some of the ways to reduce the risk of another pandemic are relatively simple, such as encouraging smallholder farmers to keep chickens or ducks away from people. Others, like improving biosecurity and introducing adequate veterinary and hygiene standards for farmed animals across the world, would require significant financial investment on a global scale. 

The 161 options include:
• Laws to prevent the mixing of different wild animals or the mixing of wild and domestic animals during transport and at markets;
• Increase switching to plant-based foods to reduce consumption of, and demand for, animal products;
• Safety protocols for caving in areas with high bat density, such as use of waterproof coveralls and masks;
• Improve animal health on farms by limiting stocking densities and ensuring high standards of veterinary care.

“We can’t completely prevent further pandemics, but there are a range of options that can substantially reduce the risk. Most zoonotic pathogens are not capable of sustained human-to-human transmission, but some can cause major epidemics. Preventing their transfer to humans is a major challenge for society and also a priority for protecting public health,” said Dr Silviu Petrovan, a veterinarian and wildlife expert from the University of Cambridge and lead author of the study. 

“Wild animals aren’t the problem - they don’t cause disease emergence. People do. At the root of the problem is human behaviour, so changing this provides the solution,” said Professor Andrew Cunningham, Deputy Director of Science at the Zoological Society of London and co-author of the study.

Solutions were focused on measures that can be put in place in society at local, regional and international scales. The study did not consider the development of vaccines and other medical and veterinary medicine options. It does not offer recommendations, but a set of options to help policy-makers and practitioners think carefully about possible courses of action. 

All categories of animal - wildlife, captive, feral, and domestic - were included in the study. The focus was on diseases, particularly viruses, which could rapidly become epidemics through high rates of human-to-human transmission once they have jumped from an animal. This excludes some well-known zoonotic diseases such as rabies and Lyme disease that require continuous transmission from animals.

The report is currently being peer reviewed. The findings were generated by a method called Solution Scanning, which uses a wide range of sources to identify a range of options for a given problem. Sources included the scientific literature, position papers by Non-Governmental Organisations, industry guidelines, experts in different fields, and the expertise of the study team itself.

This work was funded by The David and Claudia Harding Foundation, Arcadia, and MAVA.

Reference (unpublished report available as preprint)
Petrovan, S. et al: Post COVID-19: a solution scan of options for preventing future zoonotic epidemics. DOI: 10.17605/OSF.IO/5JX3G. 
 

How you can support Cambridge’s COVID-19 research

In preparation for the COVID-19 pandemic and the anticipated overwhelming demand on hospitals, the NHS moved towards of a policy of providing only essential treatments. Doctors were asked to postpone all non-urgent clinical activities including face-to-face outpatient visits, diagnostic procedures and hospital-based therapies.

As nations declared themselves ‘at war’ against the virus, they may have become blinded to the impact on other conditions. “There seems to be almost only one relevant diagnosis these days: the new virus,” writes Hensel.

This has meant that, thanks to the preparations, a major hospital could have more than 450 empty beds and less than 50% surgical theatre activity.

“The message is unmistakable: we are prepared. But this comes at a price… Antenatal care is widely reduced, cancer surgeries are limited and emergency room attendance has decreased to far less than 50% as compared with pre-coronavirus times. Where are all the sick patients that usually keep us busy?”

In fact, the level of busyness may depend entirely on the medical specialty in question. Healthcare workers in adult intensive care units face facing long hard shifts treating severely unwell patients, while most paediatric specialties are seeing a drastically decreased workload.

“Healthcare allocation, in times of COVID-19 more than ever, is a risk management game. But the ‘flatten-the-curve imperative’ inevitably comes at a price, and the bill is yet to come. As one curve is plateauing, others may even rise.”

Hensel argues that children may be getting “a bad deal” as a result of healthcare policies. They tend to have milder disease if infected, yet are missing out on other important services.

He presents the example of a two-year-old boy who was referred to his team for suspected very-early-onset inflammatory bowel disease (IBD). This is usually confirmed by endoscopy or MRI. It was only by the team successfully pressing for the boy to be considered an exception that endoscopy revealed that his symptoms were caused by a single juvenile rectal polyp (abnormal tissue growth), which was then removed. The remainder of the procedure was normal, and the boy was discharged without further medical treatment. If the team had not urged for the boy to be placed on one of the few emergency lists, he would have been mistakenly diagnosed with IBD and given immunosuppressant drugs with potential side effects while he continued to suffer symptoms.

Policies to manage resources during COVID-19 risks having a disproportionate impact on children, writes Hensel. Three months since the UK first went into lockdown, more and more negative public health consequences are beginning to unfold. Lockdown regulations and school closures are making vulnerable children even harder to reach, prompting the World Health Organization to issue a joint leaders’ statement entitled “Violence against children: a hidden crisis of the COVID-19 pandemic”.

“Tragically, detrimental social and health effects will hit the socioeconomically disadvantaged communities disproportionally harder,” writes Dr Hensel. “Food insecurity and loss of academic achievement are expected to significantly contribute to the exacerbation of the already existing inequalities.” He argues that a public health approach is urgently needed to improve child health in these challenging times, to manage domestic violence and to fight under-the-radar child neglect.

With the performance of policy-makers being judged according to internationally comparable coronavirus numbers, Dr Hensel says it is the job of physicians to speak up on behalf of underrepresented patient groups.

“We need to advocate, to give our patients a voice and to spread the message: in COVID-19 times, there is not just one diagnosis that matters.”

Reference
Hensel, KO. Double-edged sword of limiting healthcare provision for children in times of COVID-19: the hidden price we pay. BMJ; 23 June 2020; DOI: 10.1136/archdischild-2020-319575

The valve, called PoliValve, has been developed by scientists at the Universities of Cambridge and Bristol. The team’s latest in vitro results, published in the journal Biomaterials Science, suggest that the PoliValve can last for up to 25 years in patients, far longer than other types of replacement heart valves. In addition, a small pilot study in sheep showed that the valve is highly compatible with biological tissue. The researchers anticipate that the PoliValve can be tested in humans within five years.

More than 1.3 million patients with diseased heart valves need valve replacement globally each year. There are two types of artificial valves currently available, however both have limitations either in durability or in biocompatibility.

Biological valves are made from pig or cow tissue and have good biocompatibility, meaning patients do not need lifelong blood-thinning medication; however, they only last 10-12 years before failing. And mechanical valves, while they have good durability, have poor biocompatibility and patients must take daily blood-thinning drugs to prevent blood clots.

Professor Geoff Moggridge from the University of Cambridge and Professor Raimondo Ascione from the University of Bristol have spent three years conducting developmental work and testing on the PoliValve, supported by funding from the British Heart Foundation.

The device is made from a special co-polymer and is designed to resemble a natural heart valve. It was created by Professor Moggridge, Dr Marta Serrani and Dr Joanna Stasiak at Cambridge and Professor Ascione in Bristol, and builds on earlier work by Professor Maria Laura Costantino’s group at the University of Milan.

The PoliValve combines excellent durability with biocompatibility, addressing the limitations of current biological and mechanical artificial valves. It is made through a simple moulding process, which also sharply reduces manufacturing and quality control costs.

“These impressive results show the PoliValve is a promising alternative for valve replacement surgery,” said Moggridge, who leads the Structural Materials Group at Cambridge’s Department of Chemical Engineering and Biotechnology. “While further testing is needed, we think it could make a major difference to the hundreds of thousands of patients who get valve replacement surgery every year.”

According to ISO standards, a new artificial heart valve must withstand a minimum of 200 million repetitions of opening and closing during laboratory testing, equivalent to five years of life span, before it can be tested in humans. The new Cambridge-Bristol polymeric valve has comfortably surpassed this.

Initial testing in sheep has been undertaken at Bristol’s Translational Biomedical Research Centre (TBRC) facility as a first step to ensure safety. Long-term testing in sheep, also funded by the British Heart Foundation, will be carried out before bringing this new treatment to human patients.

“Patients requiring an artificial heart valve are often faced with the dilemma of choosing between a metallic or tissue valve replacement,” said Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation. “A metallic valve is long-lasting but requires the patient to take lifelong blood-thinning drugs. Although this medication prevents clots forming on the valve, it also increases the risk of serious bleeding. Patients who have a tissue valve replacement usually don’t need to take this medication. However, the valve is less durable and means the patient may face further surgery.

“The polymer valve combines the benefits of both – it is durable and would not require the need for blood-thinning drugs. While further testing is needed before this valve can be used in patients, this is a promising development, and the BHF is pleased to have supported this research.”

The PoliValve has also exceeded the requirements of ISO standards for hydrodynamic testing, showing a functional performance comparable to the best-in-class biological valve currently available on the market. The small pilot study in sheep demonstrated the device is easy to stitch in, and showed no mechanical failure, no trans-valvular regurgitation, low trans-valvular gradients, and good biocompatibility with tissue.

“The transformational PoliValve results from an advanced Bristol/Cambridge-based biomedical cross-fertilisation between experts in biomaterials, computational modelling, advanced preclinical development/testing and clinical academics understanding the patient needs. The new valve could help millions of people worldwide and we aim to test in patients within the next five years,” said Ascione.

The British Heart Foundation-funded study also included Dr James Taylor from Cambridge’s Whittle Laboratory, a team at Newcastle University headed by Professor Zaman, Professor Saadeh Sulaiman at University of Bristol and Professor Costantino’s group at Politecnico di Milano.

Reference:
Joanna R. Stasiak et al. “Design, Development, Testing at ISO standards and in-vivo feasibility study of a novel Polymeric Heart Valve Prosthesis.” Biomaterials Science (2020). DOI: 10.1039/D0BM00412J

Adapted from a University of Bristol press release. 

The study, by academics at the Faculty of Education, University of Cambridge and the LEGO Foundation, pulled together fragmentary evidence from the past 40 years to understand more about how fathers play with their children when they are very young (ages 0 to 3). The researchers wanted to find out whether father-child play differs from the way children play with their mothers, and its impact on children’s development.

Although there are many similarities between fathers and mothers overall, the findings suggest that fathers engage in more physical play even with the youngest children, opting for activities such as tickling, chasing, and piggy-back rides.

This seems to help children learn to control their feelings. It may also make them better at regulating their own behaviour later on, as they enter settings where those skills are important – especially school.

Paul Ramchandani, Professor of Play in Education, Development and Learning at the Faculty of Education, University of Cambridge, said: “It’s important not to overstate the impact of father-child play as there are limits to what the research can tell us, but it does seem that children who get a reasonable amount of playtime with their father benefit as a group.”

“At a policy level, this suggests we need structures that give fathers, as well as mothers, time and space to play with their children during those critical early years. Even today, it’s not unusual for fathers who take their child to a parent-toddler group, for example, to find that they are the only father there. A culture shift is beginning to happen, but it needs to happen more.”

Parent-child play in the first years of life is known to support essential social, cognitive and communication skills, but most research focuses on mothers and infants. Studies which investigate father-child play are often small, or do so incidentally. “Our research pulled together everything we could find on the subject, to see if we could draw any lessons,” Ramchandani said.

The Cambridge review used data from 78 studies, undertaken between 1977 and 2017 – most of them in Europe or North America. The researchers analysed the combined information for patterns about how often fathers and children play together, the nature of that play, and any possible links with children’s development.

On average, they found that most fathers play with their child every day. Even with the smallest children, however, father-child play tends to be more physical. With babies, that may simply mean picking them up or helping them to gently raise their limbs and exert their strength; with toddlers, fathers typically opt for boisterous, rough-and-tumble play, like chasing games.

In almost all the studies surveyed, there was a consistent correlation between father-child play and children’s subsequent ability to control their feelings. Children who enjoyed high-quality playtime with their fathers were less likely to exhibit hyperactivity, or emotional and behavioural problems. They also appeared to be better at controlling their aggression, and less prone to lash out at other children during disagreements at school.

The reason for this may be that the physical play fathers prefer is particularly well-suited for developing these skills.

“Physical play creates fun, exciting situations in which children have to apply self-regulation,” Ramchandani said. “You might have to control your strength, learn when things have gone too far – or maybe your father steps on your toe by accident and you feel cross!”

“It’s a safe environment in which children can practise how to respond. If they react the wrong way, they might get told off, but it’s not the end of the world – and next time they might remember to behave differently.”

The study also found some evidence that father-child play gradually increases through early childhood, then decreases during ‘middle childhood’ (ages 6 to 12). This, again, may be because physical play is particularly important for helping younger children to negotiate the challenges they encounter when they start to explore the world beyond their own home, in particular at school.

Despite the benefits of father-child play, the authors stress that children who only live with their mother need not be at a disadvantage.

“One of the things that our research points to time and again is the need to vary the types of play children have access to, and mothers can, of course, support physical play with young children as well,” Ramchandani added. “Different parents may have slightly different inclinations when it comes to playing with children, but part of being a parent is stepping outside your comfort zone. Children are likely to benefit most if they are given different ways to play and interact.”

Between 1-6% of all pregnancies in Western countries are affected by high blood pressure, which usually returns to normal after giving birth. This condition is known as gestational hypertension, or pregnancy-induced hypertension. It differs from pre-eclampsia in that traces of protein are not found in the urine. Clinicians increasingly recognise that women who have had gestational hypertension are more likely to develop cardiovascular disease in later life.

However, studies of different kinds of cardiovascular disease, such as heart disease and heart failure, have found mixed results. To examine these links further, an international team of researchers conducted a systematic review and meta-analysis of 21 studies involving a total of 3.6 million women, 128,000 of who previously had gestational hypertension. This type of study is a way of combining data from all existing relevant studies, allowing researchers to compare and consolidate results from often-contradictory studies to reach more robust conclusions.

The results are published in the Journal of the American Heart Association.

The researchers found that women who experienced high blood pressure during their first pregnancy were at 45% higher risk of overall cardiovascular disease and 46% higher risk of coronary heart disease compared to women who did not have high blood pressure in pregnancy. Women with one or more pregnancies affected by high blood pressure were at 81% higher risk of cardiovascular disease, 83% higher risk of coronary heart disease and 77% higher risk of heart failure.

“When we looked at all the available research, the answer was clear: women who develop high blood pressure during pregnancy – even when it doesn’t develop into pre-eclampsia – are more likely to develop several different kinds of cardiovascular disease,” said senior author Dr Clare Oliver-Williams from the Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge.

The study adds to growing evidence of the relationship between pregnancy and subsequent risk of cardiovascular events. Recurrent miscarriages, preterm birth, foetal growth restriction and pre-eclampsia have all previously been linked with a greater risk of heart disease.

The researchers say it is not entirely clear why gestational hypertension is associated with heart disease in later life. However, they suggest it may be that high blood pressure in pregnancy causes lasting damage that contributes to cardiovascular disease. Alternatively, women who develop gestational hypertension may have a pre-existing susceptibility to cardiovascular disease that is revealed due to the large demands that pregnancy places upon women’s bodies.

Dr Oliver-Williams added: “It’s important that women know that it isn’t their fault that they developed high blood pressure in pregnancy, and developing heart disease isn’t a foregone conclusion. Women who have experienced gestational hypertension may have been dealt a tough hand, but it’s how they play those cards that matters the most. Small positive changes can really help. They can be as simple as eating more fruit and vegetables, small bouts of regular exercise and finding time to unwind, if that’s possible with kids around.”

Dr Oliver-Williams is a Junior Research Fellow at Homerton College, University of Cambridge. The Cardiovascular Epidemiology Unit is supported by the British Heart Foundation and the Medical Research Council.

Reference
Lo, CCW & Lo, ACQ, et al. Future cardiovascular disease risk for women with gestational hypertension: a systematic review and meta-analysis. JAHA; 24 Jun 2020; DOI: 10.1161/JAHA.119.013991

Understanding how these remarkable animals are almost completely immune to cancer could improve our understanding of the early stages of the disease in people and lead to new ways to prevent or better treat it.

Until now, it was thought that naked mole-rats almost never got cancer because their healthy cells were resistant to being converted into cancer cells. However, researchers at the University of Cambridge have shown for the first time that genes known to cause cancer in cells of other rodents can also lead naked mole-rat cells to become cancerous. The results are published today in the journal Nature.

This finding suggests that what sets naked mole-rats apart is the microenvironment - the complex system of cells and molecules surrounding a cell, including the immune system. The researchers believe interactions with this microenvironment are what stops the initial stages of cancer from developing into tumours, rather than a cancer resistance mechanism within healthy cells as previously thought. 

Dr Walid Khaled, one of the senior authors of the study from the University of Cambridge's Department of Pharmacology, said: “The results were a surprise to us and have completely transformed our understanding of cancer resistance in naked mole-rats. If we can understand what’s special about these animals’ immune systems and how they protect them from cancer, we may be able to develop interventions to prevent the disease in people.”

Naked mole-rats (Heterocephalus glaber) are burrowing rodents native to East Africa. They can live for up to 37 years and are highly cancer resistant, with only a few cases ever observed in captive animals. Other unusual traits that have made them of interest to science include being the only cold-blooded mammal, lacking pain sensitivity to chemical stimuli in their skin and being able to withstand very low levels of oxygen (hypoxia). 

In the study, the researchers analysed 79 different cell lines, grown from five different tissues (intestine, kidney, pancreas, lung and skin) of 11 individual naked mole-rats. They infected cells with modified viruses to introduce cancer causing genes. These genes are known to cause cancer in mice and rat cells, but were not expected to be able to transform naked mole-rat cells into cancer cells. 

Fazal Hadi, lead researcher of the study from the Cancer Research UK Cambridge Centre, said: “To our surprise, the infected naked mole-rat cells began to multiply and rapidly form colonies in the lab. We knew from this accelerated growth that they had become cancerous.” 

The team then injected these cells into mice, and within weeks, the mice formed tumours. This striking result indicates that the environment of the naked mole-rat’s body prevents the cancer from developing, contradicting previous studies that suggested that an inherent feature of naked mole-rat cells stopped them turning cancerous in the first place. 

The scientists will now continue to investigate the mechanisms by which naked mole-rats stop cancer cells from developing into tumours. One avenue of particular interest is the unique immune system of naked mole-rats, as our immune systems play a critical role in protecting us from cancer and this power has already been effectively exploited in modern immunotherapy treatments.

Dr Ewan St. John Smith, one of the senior authors of the study from the University of Cambridge's Department of Pharmacology said: “All our work with naked mole-rats, from studying their hypoxia resistance to pain insensitivity and cancer resistance, is aiming to leverage the extreme biology of this species to understand more about how our bodies work normally.”

This research was funded by Cancer Research UK.

Reference: Hadi, F. et al; 'Transformation of naked mole-rat cells,' Nature, July 2020. DOI: 10.1038/s41586-020-2410-x

Adapted from a press release by Cancer Research UK.

Research takes place in hundreds of buildings across Cambridge, almost all of which were shut down at the end of March. The only exceptions were buildings where research related to COVID-19 was taking place, or where there were animals or plants requiring care.

“The last time the University shut down in this way was in 1665 due to the Great Plague, but Cambridge obviously looked very different then,” said Professor David Cardwell, Pro-Vice-Chancellor for Strategy and Planning. “It was an absolutely incredible effort by our staff and students to get all of our laboratories, libraries, museums and equipment quickly and safely shut down earlier this year, and now we’ve seen an even greater effort as these buildings are safely reopened.”

Cardwell is also Chair of the University’s Buildings Task Force, which has been overseeing the shutdown and reopening process. Buildings are reopening in phases, with lab-based research areas opening first. It is anticipated that the majority of research buildings, libraries and museums will be reopened by the start of Michaelmas term.

Each building needs to be individually checked for water, fire and lift safety, in addition to other basic safety checks, before it can be certified safe to open. This task has been carried out by a small team from the University’s Estates Division, who have been working around the clock to ensure that each and every building is safe to open.

“I’m incredibly proud of the work of our team in these extraordinary times,” said Graham Matthews, Director of the Estates Division. “Our top priority is making sure that our staff and students can return in a way that is as safe as possible.”

One of the first buildings to reopen was the Department of Biochemistry, which reopened to researchers on June 15. Many of the changes made to the building will be familiar to anyone who has visited a supermarket during lockdown. Stringent but creatively applied safety measures, such as clear and extensive signage, building entry and exit control and monitoring, one-way systems for footfall, single person occupancy of toilets and kitchens and the implementation of buddy systems, have allowed staff and postgraduate students to restart their research.

The University’s Botanic Garden also reopened to the public in June, and has since been overwhelmed with visitors, who have to pre-book their tickets online.

“We are delighted to have visitors back on site - it really brings the Garden to life to see people enjoying the sights and smells of the plants and to be able to hear children playing,” said Professor Beverley Glover, Director of the Cambridge University Botanic Garden. “Staff were understandably nervous at first but have really appreciated the positive atmosphere.”

Another key milestone was achieved on July 1, when the University Library began to provide limited, ‘no contact’ services for students and staff to return and pick up books ordered online, along with a new ‘scan and deliver’ service.

Intensive care specialists are like the canaries in a coalmine. They’re often the first to spot something that’s new and worrying; and it was around Christmas time last year that I remember first hearing about doctors in Wuhan, China seeing some unusual symptoms that concerned them in their patients who needed mechanical ventilation. By January I was sure that there was something very nasty heading our way.

This is the very challenge I’ve been trained for. My specialism within intensive care is in respiratory illnesses; and I had previously been part of the preparations for one of the previous waves of a coronavirus - MERS. It’s no exaggeration to say that my career has been exactly about preparing for a pandemic. I couldn’t be sure how bad it would be - but I suspected it was likely to be the biggest challenge in our lifetimes so far.  

I was chosen to lead the bronze ICU crisis team at Addenbrooke’s Hospital, which meant I was involved in the managerial and organisational challenges alongside the medical ones. We completely reconfigured the entire hospital: our starting position was 32 intensive care beds, and in mid-March there were projections that we would run out of space by the end of the month. In fact, we rapidly increased the number of beds to 84, and thankfully they have never all been full. But at times I was waking up in the night wondering “will it be enough?” It’s not just about equipment; it’s also about the vital human resources, such as having enough suitably trained nurses. We needed to rapidly train nurses about the needs of the Intensive Care Unit. 

It is incredibly complex to look after COVID-19 patients in ICU. That’s obviously because of the seriousness of their conditions - but also because we are working in full PPE. It is hot and exhausting, spending hours donned up in full gear; and throughout we have been hearing reports from around the country of medical staff themselves ending up in intensive care. But we have been fortunate in Cambridge that we always had adequate PPE, and that is partly because of wonderful collaboration with the University, which helped source supplies.   

There is no avoiding the sad fact that many of our patients die. A typical mortality rate in intensive care is around 20%, but with COVID-19 it has been more than 40% in the UK. We are dealing with something on a massive scale. Several of our patients who recovered from the virus were keen to talk to the television crews who visited the hospital, to praise the care they’d been given and some of the innovative treatments we’d been using.    

I have never at any stage regretted the career path that brought me here: not for a single minute. In some of those sleepless nights during the crisis, I have worried about whether the emergency plan would deliver in the way we hoped. But I have never doubted that I’m doing what I always intended to do, and I hope that my teams and I have made a real difference to some very poorly people.

The reaction of the public has been tremendous, too. I’d been so busy that I’d missed the start of the idea of clapping for the NHS on a Thursday night, and it was only the second time it happened that I really noticed it. I’d arrived home about five minutes before eight o’clock, and I went outside with my family. I was completely overwhelmed by the applause and the banging of pots and pans that could be heard throughout my Cambridgeshire village. This is not like me at all, but I ended up in floods of tears. It really did make a difference to know that people were behind us, and that - in these terrible times - the community was coming together.     

Charlotte Summers is a University Lecturer in Intensive Care Medicine in the Department of Medicine, and a Fellow of Selwyn College. She was awarded a Pilkington Prize in April 2020 for her commitment and excellence in teaching.

A Clap for Carers will take place this Sunday, 5 July at 5pm to mark the NHS’s 72nd birthday. 

A version of this article also appears in the Selwyn College Cambridge magazine.

How you can support Cambridge’s COVID-19 research

The dynamics of the SARS-CoV-2 pandemic share 'striking similarities' with the twin environmental crises of global heating and species extinction, argue a team of scientists and policy experts from the UK and US.

They say that lessons learned the hard way in containing COVID-19 – the need for early intervention to reduce death and economic damage; the curbing of some aspects of people’s lifestyles for the good of all of us – should also be at the heart of averting environmental catastrophe.

“We’ve seen the consequences of delayed action in the fight against COVID-19. The consequences of continued inaction in the face of catastrophic climate change and mass extinction are too grave to contemplate,” said Prof Andrew Balmford, from the University of Cambridge’s Department of Zoology.

Writing in the journal Current Biology, Balmford and colleagues argue that the spread of coronavirus shares common characteristics with both global heating and the impending 'sixth mass extinction'.

For example, each new COVID-19 case can spawn others and so lead to escalating infection rates, just as hotter climates alter ecosystems, increasing emissions of the greenhouse gases that cause warming. “Both are dangerous feedback loops,” argue the scientists.

The team also draw comparisons of what they term 'lagged impacts'. For coronavirus, the delay – or lag – before symptoms materialise means infected people spread the disease before they feel effects and change behaviour.

The researchers equate this with the lag between our destruction of habitat and eventual species extinction, as well as lags between the emissions we pump out and the full effects of global heating, such as sea-level rise. As with viral infection, behaviour change may come too late.

“Like the twin crises of extinction and climate, the SARS-CoV-2 pandemic might have seemed like a distant problem at first, one far removed from most people’s everyday lives,” said coauthor Ben Balmford from the University of Exeter.

“But left unchecked for too long, the disease has forced major changes to the way we live. The same will be true of the environmental devastation we are causing, except the consequences could be truly irreversible.”

The authors find parallels in the indifference that has long greeted warnings from the scientific community about both new zoonotic diseases and human-induced shifts in climate and habitat.

“The lagged impacts, feedback loops and complex dynamics of pandemics and environmental crises mean that identifying and responding to these challenges requires governments to listen to independent scientists,” said Dr Brendan Fisher, a coauthor from the University of Vermont. “Such voices have been tragically ignored.”

The similarities between the SARS-CoV-2 pandemic and environmental disaster lie not just in their nature but also in their mitigation, say the scientists, who write that 'there is no substitute for early action'.

The researchers include an analysis of the timing of lockdown across OECD countries, and conclude that if it had come just a week earlier then around 17,000 lives in the UK (up to 21 May 2020) would have been saved, and nearly 45,000 in the USA.

They say that, just as delayed lockdown cost thousands of lives, delayed climate action that gives us 2oC of warming rather than 1.5 will expose an estimated extra 62-457 million people – mainly the world’s poorest – to 'multi-sector climate risks' such as drought, flooding and famine.

Similarly, conservation programmes are less likely to succeed the longer they are delayed. “As wilderness disappears we see an accelerating feedback loop, as a given loss of habitat causes ever-greater species loss,” explained Princeton Professor and co-author David Wilcove.    

The scientists point out that delayed action resulting in more COVID-19 deaths will also cost those nations more in economic growth, according to IMF estimates, just as hotter and more disruptive climates will curtail economic prosperity.

Intervening to contain both the pandemic and the environmental crises requires decision-makers and citizens to act in the interests of society as a whole, argue the researchers.

“In the COVID-19 crisis we’ve seen young and working age people sacrificing education, income and social connection primarily for the benefit of older and more vulnerable people,” said co-author Prof Dame Georgina Mace from UCL.

“To stem the impacts of climate change and address biodiversity loss, wealthier and older adults will have to forgo short-term material extravagance for the benefit of the present-day poor and future generations. It’s time to keep our end of the social bargain,” Mace said.

Cambridge’s Andrew Balmford added: “Scientists are not inventing these environmental threats, just as they weren’t inventing the threat of a pandemic such as COVID-19. They are real, and they are upon us.”