New study proposes a framework for “Child Safe AI” following recent incidents which revealed that many children see chatbots as quasi-human and trustworthy.

When not designed with children’s needs in mind, Artificial intelligence (AI) chatbots have an “empathy gap” that puts young users at particular risk of distress or harm, according to a study.

The research, by a University of Cambridge academic, Dr Nomisha Kurian, urges developers and policy actors to make “child-safe AI” an urgent priority. It provides evidence that children are particularly susceptible to treating AI chatbots as lifelike, quasi-human confidantes, and that their interactions with the technology can often go awry when it fails to respond to their unique needs and vulnerabilities.

The study links that gap in understanding to recent cases in which interactions with AI led to potentially dangerous situations for young users. They include an incident in 2021, when Amazon’s AI voice assistant, Alexa, instructed a 10-year-old to touch a live electrical plug with a coin. Last year, Snapchat’s My AI gave adult researchers posing as a 13-year-old girl tips on how to lose her virginity to a 31-year-old.

Both companies responded by implementing safety measures, but the study says there is also a need to be proactive in the long-term to ensure that AI is child-safe. It offers a 28-item framework to help companies, teachers, school leaders, parents, developers and policy actors think systematically about how to keep younger users safe when they “talk” to AI chatbots.

Dr Kurian conducted the research while completing a PhD on child wellbeing at the Faculty of Education, University of Cambridge. She is now based in the Department of Sociology at Cambridge. Writing in the journal Learning, Media and Technology, she argues that AI has huge potential, which deepens the need to “innovate responsibly”.

“Children are probably AI’s most overlooked stakeholders,” Dr Kurian said. “Very few developers and companies currently have well-established policies on how child-safe AI looks and sounds. That is understandable because people have only recently started using this technology on a large scale for free. But now that they are, rather than having companies self-correct after children have been put at risk, child safety should inform the entire design cycle to lower the risk of dangerous incidents occurring.”

Kurian’s study examined real-life cases where the interactions between AI and  children, or adult researchers posing as children, exposed potential risks. It analysed these cases using insights from computer science about how the large language models (LLMs) in conversational generative AI function, alongside evidence about children’s cognitive, social and emotional development.

LLMs have been described as “stochastic parrots”: a reference to the fact that they currently use statistical probability to mimic language patterns without necessarily understanding them. A similar method underpins how they respond to emotions.

This means that even though chatbots have remarkable language abilities, they may handle the abstract, emotional and unpredictable aspects of conversation poorly; a problem that Kurian characterises as their “empathy gap”. They may have particular trouble responding to children, who are still developing linguistically and often use unusual speech patterns or ambiguous phrases. Children are also often more inclined than adults to confide sensitive personal information.

Despite this, children are much more likely than adults to treat chatbots as if they are human. Recent research found that children will disclose more about their own mental health to a friendly-looking robot than to an adult. Kurian’s study suggests that many chatbots’ friendly and lifelike designs similarly encourage children to trust them, even though AI may not understand their feelings or needs.

“Making a chatbot sound human can help the user get more benefits out of it, since it sounds more engaging, appealing and easy to understand,” Kurian said. “But for a child, it is very hard to draw a rigid, rational boundary between something that sounds human, and the reality that it may not be capable of forming a proper emotional bond.”

Her study suggests that these challenges are evidenced in reported cases such as the Alexa and MyAI incidents, where chatbots made persuasive but potentially harmful suggestions to young users.

In the same study in which MyAI advised a (supposed) teenager on how to lose her virginity, researchers were able to obtain tips on hiding alcohol and drugs, and concealing Snapchat conversations from their “parents”. In a separate reported interaction with Microsoft’s Bing chatbot, a tool which was designed to be adolescent-friendly, the AI became aggressive and started gaslighting a user who was asking about cinema screenings.
 
While adults may find this behaviour intriguing or even funny, Kurian’s study argues that it is potentially confusing and distressing for children, who may trust a chatbot as a friend or confidante. Children’s chatbot use is often informal and poorly monitored. Research by the nonprofit organisation Common Sense Media has found that 50% of students aged 12-18 have used Chat GPT for school, but only 26% of parents are aware of them doing so.

Kurian argues that clear principles for best practice that draw on the science of child development will help companies keep children safe, since developers who are locked into a commercial arms race to dominate the AI market may otherwise lack sufficient support and guidance around catering to their youngest users.

Her study adds that the empathy gap does not negate the technology’s potential. “AI can be an incredible ally for children when designed with their needs in mind – for example, we are already seeing the use of machine learning to reunite missing children with their families and some exciting innovations in giving children personalised learning companions. The question is not about banning children from using AI, but how to make it safe to help them get the most value from it,” she said.

The study therefore proposes a framework of 28 questions to help educators, researchers, policy actors, families and developers evaluate and enhance the safety of new AI tools.

For teachers and researchers, these prompts address issues such as how well new chatbots understand and interpret children’s speech patterns; whether they have content filters and built-in monitoring; and whether they encourage children to seek help from a responsible adult on sensitive issues.

The framework urges developers to take a child-centred approach to design, by working closely with educators, child safety experts and young people themselves, throughout the design cycle. “Assessing these technologies in advance is crucial,” Kurian said. “We cannot just rely on young children to tell us about negative experiences after the fact. A more proactive approach is necessary. The future of responsible AI depends on protecting its youngest users.”

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Survey highlights public’s hopes for the future of cancer research and care

By Craig Brierley

• Late detection is the biggest worry in relation to cancer diagnosis, with 55% of people wanting to see future advances in early cancer detection
• The public overwhelmingly support the use of AI to tackle cancer
• 43% of people recognise the major impact universities can have on reducing deaths from cancer

Two-thirds of the public say they are very or somewhat worried about being told they have the disease – higher than for any other medical condition, including dementia and having a heart attack – according to polling released today.

The survey, carried out among 2,000 UK adults by Public First on behalf of the University of Cambridge, highlights the concerns that people have over a cancer diagnosis. It suggests that late diagnosis – too late to treat their cancer – is the biggest concern in relation to a cancer diagnosis (70%) followed by the impact on one’s family and those around them (52%).

When asked which transformative development they would like to see in the future – including eradicating diseases such as malaria, self-driving cars becoming commonplace, and genetically engineered crops enabling us to end famine – 55% of respondents chose “being able to detect and treat cancer early enough so that no-one dies of the disease”. Only eliminating poverty came anywhere close, with 23% of respondents.

The University of Cambridge and its partner Cambridge University Hospitals NHS Foundation Trust (CUH) are working to build Cambridge Cancer Research Hospital, a revolutionary new type of hospital that promises to change the story of cancer. The specialist cancer facility is bringing world-leading scientists within the walls of a new NHS hospital – for the first time – to detect cancer earlier and deliver personalised healthcare and precision cancer medicine to patients.

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Artist’s impression of Cambridge Cancer Research Hospital on the Cambridge Biomedical Campus

“Cancer affects one in two of us and understandably induces fear in patients and their families. People are worried that treatments won’t work or that the side-effects will be terrible, but also what their diagnosis will mean to their family.

“At Cambridge we believe it’s possible to imagine a world where there is no longer a fear of cancer. It’s an ambitious goal that we – along with many other researchers around the world – are working hard to realise.”

^{Professor Richard Gilbertson, Director of the Cancer Research UK Cambridge Centre}

Professor Rebecca Fitzgerald demonstrates the capsule sponge for early detection of oesophageal cancer

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When asked what would concern them most about receiving a cancer diagnosis, the most commonly selected worry was that the cancer would be detected too late to treat (70%). 52% of respondents were concerned about the impact on their family or those around them, 41% about getting access to the right treatment, and 36% about the side-effects of treatments.

Asked what would make them less afraid of being diagnosed with cancer, 61% replied “Knowing that the form of cancer I have is treatable”. Highlighting once again the importance of early detection, over half of respondents (51%) said “Knowing we are better at catching cancer early enough to treat”.

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“Outcomes can be completely transformed – better survival and less invasive treatments – if the cancer is diagnosed early enough. That’s why a lot of our focus now is on understanding cancer at its very earliest stage – years before an individual will develop any symptoms.

“That way, it may even be possible to prevent the disease in the first place, or at least catch it when it can be treated easily.”

^{Professor Rebecca Fitzgerald, Director of the Li Ka Shing Early Cancer Institute}

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Knowing that a lot of people – including organisations such as the University of Cambridge – are researching how we prevent, diagnose and treat cancer is reassuring, the poll suggests. A third of respondents (32%) said this would make them less afraid of a cancer diagnosis. 43% of respondents believe cancer research at universities will have a big impact on reducing deaths from cancer (though perhaps unsurprisingly, 64% thought the biggest impact on reducing cancer deaths would come by reducing NHS waiting times).

Professor Steve Jackson, who developed the life-saving cancer drug olaparib

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“Cambridge is really leading the way on transforming our understanding of cancer and how we can prevent it and treat it. This brilliant work will save and transform lives locally, nationally, and around the world, such as being able to sequence a tumour’s DNA at speed right through to developing revolutionary new cancer drugs such as olaparib. It is world-leading work which makes me extremely proud.”

^{Professor Deborah Prentice, the Vice-Chancellor of the University of Cambridge}

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Dr Raj Jena, who has pioneered the use of AI in preparing radiolotherapy scans, saving many hours of doctors’ time

The public were asked their views on the use of artificial intelligence (AI) to improve diagnosis and treatment of cancer. An overwhelming majority were in favour of its application, with just 8% saying we shouldn’t use AI for cancer diagnosis and treatment. 55% thought it was acceptable to use AI to speed up research into new treatments, 47% to help a doctor diagnose their cancer and 41% to help their doctor decide which treatment would work best.

At the University of Cambridge, scientists are developing AI tools with the potential to transform cancer treatments, by speeding up diagnosis, personalising therapy, and reducing costs. As part of this work, researchers are using AI to predict how patients will respond to a particular treatment before they receive it, allow them to start treatment sooner, target hard-to-treat cancers, and enable screening of cancers that at the moment would otherwise be prohibitively expensive.

When presented with a number of undesirable future events, a cancer diagnosis was second only to the death of a close relative in terms of being most worrying (64% verses 72%) – higher than nuclear war (56%), terrorism (53%) and being a victim of crime (52%). Surprisingly, older age groups were significantly less likely to say they were “very worried” about cancer compared to younger age groups – 14% of over 65s compared to 26% of 18-24 years olds and 29% of 25-34 year olds.

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The University of Cambridge is currently fundraising for the Cambridge Cancer Research Hospital. To support this, it is launching a month-long focus on its cancer research, including a look at the new hospital, meeting researchers studying the earliest stages of cancer, finding out how AI is helping in the fight against the disease, and meeting some of the patients who are playing a key role in groundbreaking cancer research.

Find out more at Cambridge is Changing the Story of Cancer

Cambridge Cancer Research Hospital

By Craig Brierley

Architect’s image of Cambridge Cancer Research Hospital

Work will begin soon on a new hospital that will transform how we diagnose and treat cancer. Cambridge Cancer Research Hospital will treat patients across the East of England, but the research that takes place there promises to change the lives of cancer patients across the UK and beyond.

Professor Richard Gilbertson

Dr Hugo Ford

Standing on the rooftop of the Cancer Research UK Cambridge Institute, Professor Richard Gilbertson points to an unassuming car park below, nestled between the institute and global pharmaceutical giant AstraZeneca.

“That’s where the new hospital will be,” he says.

It’s hard to envisage that in just a few years’ time, this will be the location of Cambridge Cancer Research Hospital, a radical new hospital that promises to change the story of cancer forever. It will be funded two-thirds by Government and one-third by philanthropy, with £100m to be raised jointly by the University of Cambridge and Addenbrooke’s Charitable Trust.

The Hospital – a collaboration between the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust – will have 77 single inpatient rooms, along with a significantly expanded outpatient department and larger day patient unit.

But what really sets it apart is that in the same building, alongside the patients and their medical teams, will be academic and industry researchers, focused on delivering solutions that will transform the lives of millions of cancer patients – not just in the Cambridge and the East of England, but worldwide.

“At the moment, cancer affects one in two of us and is a diagnosis that induces fear in patients and their families,” says Gilbertson, Director of the Cancer Research UK Cambridge Centre and Research Lead for Cambridge Cancer Research Hospital. He is responsible for ensuring that research is at the heart of everything that takes place there.

“But imagine a world where there is no longer a fear of cancer. That’s the world we’re trying to create.”

Dr Hugo Ford, Head of Cancer Services at CUH and Clinical Lead for Cambridge Cancer Research Hospital, says that bringing academics and doctors together is about “maximising the clinical benefits, the real world benefits of the research that’s done. And we’re trying to bring in other communities from industry, from biotech, from other university departments, to build a much wider community.”

Catching cancer early

One of the main focus areas for the new hospital is an area in which Cambridge has built unique expertise: early detection and intervention.

“We know that for a lot of cancers there is a latency period where they’re either in a precancerous stage or in an early cancer stage before it can ever be diagnosed by conventional methods,” says Ford. Are there ways to detect the cancer at this early stage and intervene?

Gilbertson says such an approach will present a ‘win-win’ for both patients and the NHS. “If you detect the cancer early, the survival chances are much better and the treatment needed is generally easier and more straightforward. This is better for patients and much less expensive for the NHS.”

The top floor of the future hospital will house the Early Cancer Institute Research Clinic, headed by Professor Rebecca Fitzgerald, a clinical researcher who spends part of her time looking after patients with oesophageal cancer, a cancer that is difficult to treat if not caught early.

“We’re being much more proactive,” says Fitzgerald. “We’re trying to predict who needs more careful monitoring or preventative action ahead of them even knowing they’ve got a problem.”

This will make Cambridge Cancer Research Hospital the only hospital in the UK that has space specifically aimed at preventing cancer, she says. “It’s really a testament to putting faith in the fact that we think there are different ways of doing things for the future.”

Fitzgerald already heads the Early Cancer Institute across the Campus, which is undergoing redevelopment as the Li Ka Shing Early Cancer Institute to enable world-class fundamental research aimed at understanding how cancers emerge and develop, finding biomarkers to detect it, and developing new strategies to find people at risk and to intervene.

She says the new Research Clinic in the hospital will enable them to translate their discoveries into clinical practice. On the top floor it will have space for healthy and pre-symptomatic individuals to take part in studies as well as a “hotel type of arrangement” where researchers from across Cambridge and beyond – often from disciplines outside medicine, such as physics, engineering and maths – are able to spend a period of time working in partnership with patients to develop and test their innovations.

“The best way to really get research done in the most efficient way is to have it right alongside the patient,” she says. “The closer you can bring these things together, to really embed it in the whole ecosystem, it makes it easier for the researchers, it makes it easier for the patients.”

Developing a diagnostic test can be a long and laborious process. Fitzgerald knows this only too well. Her capsule sponge for diagnosing Barrett’s oesophagus, a condition that greatly increases the risk of oesophageal cancer, is in the final stages of testing before being rolled out across the NHS, but it has taken two decades to reach this stage.

The hospital has carried out economic modelling that shows how having researchers in geographically dispersed locations – even just across the city, as is the case with Cambridge – can significantly hamper innovation.

“Even for some of the more straightforward inventions that we’ve invented here, particularly in early detection, could have been developed years faster had scientists been located next to patients,” says Gilbertson, who is also Chair of the NHS Innovation External Advisory Board, and so is familiar with the challenges of bringing innovations into the NHS.

“To change the story of cancer, there needs to be a seamless integration between research and NHS care,” he explains. “We’re seeking to take the very best of Cambridge science and make sure it’s ‘NHS ready’, ensuring it can be readily deployed in York, Hartlepool, Stockport, wherever, patients need it.”

Professor Rebecca Fitzgerald with the capsule on a string

Professor Jean Abraham

Kinder, faster treatments

While the ambition is to catch cancer early enough to cure it – and ultimately, to intervene early enough to prevent it – there will always be patients needing more intensive or longer-term treatment.

In the past, cancer treatments brought with them extremely unpleasant side-effects, but thanks to new generations of medicines and therapies – including so-called PARP inhibitors developed here in Cambridge – treatments can be much more targeted, making them more effective and with fewer side-effects.

Professor Jean Abraham directs the Precision Breast Cancer Institute, which will move into Cambridge Cancer Research Hospital. Abraham and her team use the latest advances in genomics to better match treatment to particular changes in DNA that give rise to the tumour. Once a patient is undergoing treatment, they hope to monitor almost in real time how the tumour is responding – is it shrinking in response to the drugs, for example – and adjust as necessary.

“One of the great things that will happen when we get into the hospital is that we’ll have the Precision Breast Cancer Institute and side-by-side to that will be our NHS Breast Cancer Unit for our patients,” she says.

Equally exciting, she says, is that next to these will be the Integrated Cancer Medicine Institute. There, researchers will look for ways to bring together the many different data sets collected from cancer patients – from DNA to blood tests and biopsies to medical imaging, for example – and apply artificial intelligence (AI) to guide treatment options.

Gilbertson says this will help them completely transform the currently “very clunky” patient pathway that starts with the patient noticing something is wrong and getting referred by their GP to their local hospital where doctors will run a number of tests.

“Those tests are like a hand of cards,” he says. “Doctors currently hold in their hands a bunch of x-rays, blood tests, DNA sequencing, histology, and clinical information and try to compare these to make decisions.

“Comparing these very different pieces of information is hard, and currently involves a group of very smart and very busy people sitting in a room – nurses, doctors, surgeons, radiologists, pathologists – spending many hours trying to make sense of these data for 50 or so patients at a time. You can imagine that this takes hours and is very inefficient.”

Multiply this process across the NHS and it creates “massive workforce issues and inefficiencies. But if we could harness the power of AI to read scans, read histology reports, look at genomic data, and importantly integrate all this data, then this could transform the speed, accuracy and efficiency to make real time clinical decisions for 40 of those 50 patients.

“This doesn’t take the doctor out of the picture. Most likely it will provide rapid answers for the 30-40 patients who have more straightforward treatment options, freeing the team to discuss the mode complex and difficult cases.”

Listening to the voices of patients

Crucial to the development of Cambridge Cancer Research Hospital has been the involvement of patients – after all, its entire ethos is about improving their lives.

Ensuring that their voices are heard is the responsibility of Elaine Chapman, the Lead Advisory Nurse on the project and herself a person living with breast cancer.

“I see very much part of my role as helping us work out how we’re going to make this building work in practice on a day-to-day basis. So for patients, that’s about thinking what experience, what things they might be feeling and thinking when they’re coming to the building and how can we have an environment that will help them to feel comfortable?”

Chapman is the liaison with the Patient Advisory Group, co-chaired by Fiona Carey and Neil Stutchbury.

“We’re trying to change the experience for cancer patients and make it better,” says Carey, who took early retirement in 2012 following her third major surgery, which was for kidney metastases in the pancreas, which took a huge toll on her. “You wouldn’t build a Cineplex without talking to people who are going to use it. If you have your patients around the table from the beginning, you’re going to avoid costly mistakes.”

Patients have been heavily involved in the design and building of the new hospital from the start, sitting on all the working groups, alongside the professionals.

“We see things clinicians don’t see,” says Carey. “We know things they don’t know. And patients aren’t just patients. They have skills and expertise. They might be engineers, architects, accountants, artists – we all bring stuff into the room beyond what would have been there without us.”

Patients groups have been involved in the hospital project since very early on. This has resulted in important changes to the proposed design, such as having changing rooms and procedure rooms connected by a door rather than across a public corridor.

“We all know about gowns,” says Carey. “The whole thing is really awkward. Should I wear shoes and socks? Is my bum hanging out the back? Now the design has been changed to remove that problem.”

Chapman says there is great enthusiasm for the project among the patients she speaks to. “This new way of doing things, having those University institutes integrated into the building so that research can go from a thought straight to a patient is incredibly inspiring.”

Fiona Carey

Elaine Chapman

Great expectations

Work will begin imminently on the new specialist hospital within the burgeoning Cambridge Biomedical Campus, which is itself located at the heart of the UK’s and Europe’s leading life sciences cluster.

It’s anticipated that Cambridge Cancer Research Hospital will open its doors to patients, doctors and researchers in 2029. For everyone involved, it cannot come soon enough.

“We already do amazing things in Cambridge,” says Chapman. “But by having a new building that has been designed in partnership with patients, clinicians and the University, we’ll improve the experience for those working in there and for our patients coming to it.”

Ford believes that the atmosphere that they will create in the new hospital will make it feel like “a place that people want to come and work at, and feel that what they do is changing people’s lives“.

As a practising clinician, he says that for the first time in his career, he looks forward to being able to offer people treatment in an environment that genuinely contributes to their health and well-being.

There’s a lot of evidence about the impact of the environment on the patients, he says. “It makes a difference to how they feel about their treatments and it makes a big difference to the way that the staff approach their work. Ultimately, the environment makes a major contribution to successful patient outcomes.“

The ambition is for the hospital’s impact to resonate far beyond its four walls, says Abraham.

“We can change the outcomes and the way we care for our breast cancer and other cancer patients, both here and around the world,” she says. “What we want to develop are tools and ways in which we can help not just local patients, but regional, national and international patients. We know we can deliver this because of networks of centres who have worked with us nationally and internationally on a variety of studies who we will partner with to increase our global impact.”

All of this is possible, says Gilbertson, because Cambridge is “a magnet for brilliance” that spans across the disciplines and from which the Hospital can draw expertise.

“By uniting the brilliance of Cambridge with our patients, we can totally transform the way we practice medicine,” he says. “Cambridge is a special place. In fact, it’s a special place for the country and beyond. Our vision is not just for the NHS – it reaches to other countries. It’s a unique time to achieve that.”

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The University would be grateful to hear from people, trusts and foundations interested in providing significant philanthropic support for the hospital. Please contact Mary Jane Boland, Director of Development, Cambridge University Health Partners.

A life-saving cancer therapy is being scaled up in Cambridge to deliver more treatments to more patients for more cancers.

It works by super-charging the patient’s own immune system.

By Louise Walsh

Illustration of T cells (purple) attacking cancer cells (green)

Our immune system has billions of ‘T cells’ which recognise and destroy cells that might pose a threat to our wellbeing, such as those that show specific hallmarks of infection and disease. But these remarkable cells appear to be outwitted by cancer cells, which evade detection and grow uncontrollably.

CAR-T is a type of immunotherapy that provides a way round this by turning a patient’s own T cells into a battalion of highly targeted killers.

In 2020, Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust, became one of only a small number of centres in England equipped to provide this complex treatment.

For some of these patients, the treatment has cured them of their cancer.

“CAR-T cell therapy is a ‘living treatment’ in that once the cells are given to a patient, they persist for many months or even years, ready to attack the cancer cells should they pop up again,” explains Dr Ben Uttenthal, clinical lead for immune effector cell therapies at Addenbrooke’s and the Cancer Research UK (CRUK) Cambridge Centre’s Cancer Immunology Programme.

“For some types of aggressive cancer we are finding that we can cure more than double the number of patients using CAR-T cell therapy. It’s been a game-changing treatment – and we’re only just scratching the surface of what’s possible.

“All the parts of the jigsaw are now coming together to develop newer and better therapies in Cambridge so that we can get more people back into the life they want to live.”

What is CAR-T cell therapy?

Blood is collected from the patient and their T cells are isolated.

The T cells are then reprogrammed to carry a protein called the chimeric antigen receptor (CAR), which recognises certain cancer cells.

These modified CAR-T cells are then grown into large numbers and given back to the patient.

When the CAR-T cell spots a cancer cell, it starts to multiply and attract other parts of the immune system to attack and kill the cancer.

A ‘living treatment’ for patients

After receiving CAR-T cell therapy at Addenbrooke’s Hospital, one patient credited the treatment with saving his life.  

“I was basically told there was nothing else that could be done [for my leukaemia] as far as conventional medicines were concerned. It was at this point my consultant told me about a new trial that was taking place known as CAR-T cell therapy. For me it was the last chance saloon,” said Steve Johnson.

“Having the treatment is not pleasant – I had a number of fevers and temperature spikes for two weeks after the CAR-T cells were put back in, but I have absolutely no doubt this treatment saved my life.”

So far, only some types of blood cancers have been approved for CAR-T cell therapy by the NHS, explains Uttenthal: “The pioneering treatment is currently being offered to patients with aggressive forms of blood cancer called B-cell lymphoma and acute lymphoblastic leukaemia who have either relapsed or not responded well to chemotherapy or stem cell treatment.”

One such patient was a 54-year-old woman with a B-cell lymphoma which had shown no response to several different types of chemotherapy.

“After we infused the CAR-T cells back into her, the cells became activated and attacked her lymphoma,” says Uttenthal.

“The reaction was so vigorous that at one point we needed to give an antidote to damp down the immune response. She needed intensive monitoring for a time, but after a couple of weeks she improved and she’s now completely recovered. The last time we spoke she was away on a golfing trip in the Mediterranean!”

The number of patients who can benefit from CAR-T cell therapy is increasing, explains Uttenthal: “That’s partly because the success of CAR-T cells has meant that they are being brought to earlier lines of treatment.

“But we want to increase this yet further by implementing CAR-T cell therapy for other kinds of cancer, and by making CAR-T cells that have fewer side effects so that they can be given in less specialist centres.”

To improve CAR-T cell therapy further needs experts like Dr Mike Chapman, whose work at the MRC Toxicology Unit in Cambridge has focussed on identifying new targets and reducing toxicity.

New targets, less toxicity

Dr Mike Chapman is an expert in proteomics – the study of the interactions and structures of proteins and their cellular activities – and is the “academic driver behind what we do” says Uttenthal.

One focus of Chapman’s work has been myeloma, a cancer of a type of white blood cell called plasma cells. “Although CAR-T cells have been developed for this cancer, they haven’t yet given the long-term responses that we have seen in other blood cancers,” he explains.

Taking samples of tumour from patients with myeloma, Chapman has been using proteomic techniques to map and quantify the many thousands of proteins on the surface of these cells – and then using computational approaches to prioritise and select them as potential targets.

Having multiple targets will be better than just one, adds Chapman, “otherwise, the cancer will always find ways to escape.”

He is currently working with CRUK’s innovation arm, Cancer Research Horizons, to progress the most advanced of the targets he’s identified into effective treatments for cancer patients.

“There’s a predictability about CAR-T cell therapy,” adds Chapman.

“With blood cancers, if you know the target on the cancer cell and you can make the CAR-T cell that will target it, then these living therapies are essentially curative. And we also know that if some off-target killing of normal blood cells happens then the patient’s blood system copes well.”

But, in the case of myelomas, current therapies have run into problems whereby the CAR-T cell accidentally targets cells in the brain tissue. Chapman is working on a potential solution: ‘on-off gates’.

“We can make CAR-T constructs clever enough to switch themselves off if they recognise a marker that identifies it as the wrong cell to kill – like a brain cell,” he explains.

“But we’re taking this a stage further by re-wiring the cell to attack cancer cells that express only low levels of the target. It’s a complicated system but the great thing about CAR-T cells is it’s a ‘rational therapy’ – what you predict happens actually does happen.”

Making CAR-T ‘in house’

CAR-T therapy is expensive because both the engineering of the cells and the manufacturing is carried out by specialist companies. Sarah Albon is looking to bring this home.

Albon is the director of the Cambridge Cellular Therapy Laboratory (CCTL) at Addenbrooke’s Hospital. She leads a team with expertise in immunotherapies and delivering bone marrow and stem cell transplants across the whole of the East of England.

“That’s CCTL’s ‘bread-and-butter’ job,” she says. “But we also act as a regulated cell handler for a number of other novel cell therapy products – particularly those that have just come onto the market like CAR-T cells.”

Currently, the CAR-T cell therapies are manufactured by large pharmaceutical companies. Albon’s team delivers the patient cells to the manufacturer and then receives and stores the final T cell product ready for when the patient needs it.

“These novel products are made specifically for each patient from their own cells, so we have to be 100% sure they are what we think they are to make sure that each patient receives the correct treatment. This is why the work we do in CCTL is highly regulated.”

A state-of-the-art clean room suite is being built on the Addenbrooke’s site that will expand the facilities of CCTL significantly. The aim is to deliver more treatments to more patients for more cancers, in readiness for the planned Cambridge Cancer Research Hospital being built.

The expansion will also mean a greater capacity to be involved in clinical trials.

“A CAR-T might be licenced for use in acute lymphoblastic leukaemia for example, but in order for that same product to be used in a different malignancy, it would have to undergo a clinical trial in that patient population. Then the manufacturer gathers the data and applies for a licence,” she explains.

“We already work closely with the Cambridge Clinical Trials Centre at Addenbrooke’s on CAR-T trials and we will be expanding this once the new labs are up and running.

“Our ultimate goal is to manufacture our own CAR-Ts in our own laboratories here in Cambridge. The expertise and infrastructure are in place, and our new expanded facilities will enable us to do that. It’s now within reach.”

Professor Sir Steve Jackson on how his research led to a life-saving cancer drug

By Louise Walsh

The drug olaparib has now been used to treat over 140,000 patients globally, changing the outlook for people with breast, ovarian, prostate and pancreatic cancers.

We talk to Professor Sir Steve Jackson about chance, risk, curiosity and shots-on-goal in the journey of his discovery.

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Steve admits he can be a bit evangelical about DNA repair.

For the past 35 years in Cambridge, he and his team have explored how our cells are able to deal with damage to our DNA.

Thanks to his and others’ work we now know that an orchestrated network of ‘molecular police’ patrol, recognise and repair mistakes in our DNA caused either by accident or by agents like UV light or carcinogens. DNA repair keeps our genetic material intact so that it can carry on encoding the functions necessary for life.

But Steve’s fundamental curiosity about the nitty-gritty of DNA repair also led him in what he describes as “wonderfully unforeseen directions”.

After a chance observation and a leap of thinking, he realised that it was possible to switch off certain DNA repair mechanisms in cancer cells, causing them to die, while normal cells “just shrugged their shoulders and carried on growing and dividing”.

This led to him setting up a team of scientists in 1999 that created olaparib, a new class of cancer drug, which has now been used to treat over 140,000 patients globally. One of these patients is Jackie van Bochoven.

Jackie’s story

Jackie was diagnosed with BRCA1 breast cancer in February 2019. She was having yearly mammograms because of her family history of cancer and her tumour was caught early. But, although it was small, the cancer was very aggressive. She tells us what happened next:

“When I had the diagnosis, I was shocked and numb. There were so many things going through my head. I thought about my children. And I thought about my mum and my sister who had both been diagnosed with breast cancer.

After the initial biopsy, I met Professor Jean Abraham at Addenbrooke’s Hospital in Cambridge and she thought I was a good candidate for a new trial for breast cancer involving a combination of chemotherapy and olaparib.

I felt it was a fantastic opportunity. I was thinking about my family and future generations. I felt it was important to be part of the trial.

Five years on, I’ve just found out this week [April 2024] that the trial’s been very successful. I’m back at work. I’m enjoying life. The trial has made a huge difference, and the success rate has been really positive for me. I’m taking every day as it comes and taking every opportunity that I can.”

Steve’s story

What excites Steve is understanding how biology works and why it sometimes goes wrong. But what galvanises him, he says, is knowing there are people alive today as a result of his “counterintuitive” discovery of how to create a cancer drug:

I’m a scientist so I haven’t tended to come into contact with patients who my work has helped. But it’s such a privilege when I have. One lady I met a few years ago stays in my mind. Her ovarian cancer had returned and she was offered olaparib as part of a trial. She described how frightening it was to be trying something so new but felt it was her only hope. The drug worked and when we met, she had no signs of the cancer.

She said that I’d given her life back to her. I don’t tend to think of myself as a lifesaver but it’s probably no surprise that I consider the development of olaparib as the most meaningful outcome in my career so far.

When I started out as an independent group leader in Cambridge, nearly everything my group touched seemed to turn to gold. And then a reviewer’s comment made me stop and think. I had brilliant people in my lab at the Gurdon Institute, where I was based when I moved to Cambridge in 1991. We were working in new areas, studying how genes are transcribed into RNA to make proteins and we also had first insights into other cellular processes. We had a brilliant review from our funders at the end of the first five years, but one of the comments questioned whether it was relevant for cancer patients.

I was concerned that great research on its own might not be fundable. We needed to find translational opportunities that would potentially benefit patients.

Meanwhile I’d stumbled across something new and interesting: an enzyme that was activated by breaks in DNA. It took a little time for the penny to drop but, when it did, I realised that something activated by broken DNA is probably involved in DNA repair. The enzyme was part of a ‘molecular police force’ that patrols, spots damage and triggers the fixing processes.

“My Eureka moments?

A counterintuitive idea and a late-night conversation in a bar.”

This started cogs whirring in my brain. I knew that radiation and chemotherapies kill cancer cells by generating DNA damage. Could we make drugs that stop the molecular police from repairing the damage?

I couldn’t get people to buy into the idea… why would you want to inhibit DNA repair? We need DNA repair. It was counterintuitive to think about knocking it out.

One of the great things about Cambridge is that there are lots of examples of very successful biotech start-ups. I thought, if they can do it, why can’t I? And that’s the story of KuDOS, the company I set up in 1997. I was a young professor in Cambridge and the science was new, but a small set of venture capital groups had the confidence to back me in my ideas. Crucially I also had the support of my funders (the predecessors of Cancer Research UK) and the Tech Transfer Office (now Cambridge Enterprise).

The game plan was to go all-out and develop drugs against DNA repair enzymes, including against a protein family called poly ADP-ribose polymerase (PARP) which we knew helped repair broken DNA. Out of this programme came olaparib, a potent PARP inhibitor.

“There’s something about the environment here in Cambridge that not only creates great science. It also really nurtures people and connections.”

And then came the second Eureka moment. I was at a conference in a late night bar talking to Professor Alan Ashworth who at the time was at the Institute for Cancer Research in London. He was working on cells with mutations in genes called BRCA1 and BRCA2, which commonly occur in people with cancer.

DNA repair is so important to our survival that we have evolved a backup mechanism in case PARP fails. One such process is called homologous recombination and it involves DNA being exchanged between identical pieces of DNA to repair it.

Alan and others had figured out that BRCA1 and BRCA2 are very important for homologous recombination. We speculated that if you block the PARP repair mechanism in people with cancers caused by BRCA1/2 defects, their healthy cells might revert to their backup and survive but, because the tumour cells have no BRCA1 or 2, they may have no backup and so would die. This is exactly what scientists in our groups found.

This was the answer. It meant that the PARP inhibitors that KuDOS had developed could be used to treat patients who had BRCA1/2-mutated cancers. Sure enough, when we tested this, the BRCA-deficient cells dropped dead when you gave them a PARP inhibitor at concentrations where normal cells just shrugged their shoulders and carried on growing and dividing.

We published our work in the journal Nature in 2005. It took us almost 18 months to get it through the reviewers. It wasn’t that they didn’t believe it. They were saying – at least for a while – was this really all that exciting and interesting?

Meanwhile, work was moving fast at KuDOS. Olaparib had already gone into healthy volunteers. The next stages of clinical trials were going to be very expensive. The best way forward would be either to partner with a pharmaceutical company to share the risk and share the benefit, or to be acquired by a pharma company, which is what we did. AstraZeneca bought KuDOS in 2006 for $210m.

“I consider olaparib as the most meaningful outcome in my career so far.”

This year marks 10 years since the European Commission granted approval for olaparib, marketed as Lynparza (the trade-name of olaparib) by AstraZeneca, to treat ovarian cancer patients who have BRCA1 or BRCA2 mutations. The drug has been jointly developed and commercialised by AstraZeneca and MSD, and is now approved in several countries across multiple tumour types including forms of breast cancer, pancreatic cancer and prostate cancer.

Then, in 2023, the NHS agreed a deal to roll-out the drug to treat advanced prostate cancer and a form of early breast cancer.

I’m now based at the Cancer Research UK (CRUK) Cambridge Institute, which is next door both to AstraZeneca’s European headquarters and Addenbrooke’s Hospital on the Cambridge Biomedical Campus. I pass clinicians in the Institute corridor who prescribe olaparib for their patients. It’s nearly 35 years since I set up my lab in Cambridge and I oscillate between thinking the time has gone in a flash to thinking it’s been a long slog which nearly did me in!

One thing I’ve learned is that ideas need people to drive them over lines. In particular my KuDOS colleagues Niall Martin, Graeme Smith, Keith Menear and Barrie Ward, as well as Mark O’Connor who brought huge continuity to the drug’s development when he moved to AstraZeneca from KuDOS when it was acquired, and Susan Galbraith at AstraZeneca who had the insight and gravitas to allow the programme to progress. There’s something about the environment here in Cambridge that not only creates great science. It also really nurtures people and connections.

Curiosity is also hugely important. There are a great many things we don’t know and many things we don’t even know we don’t know. The possibility of scientific discovery is what gets me out of bed in the morning.

Science is moving ever more quickly now. I’m hopeful that more of these kinds of drugs will find their way to the right patients in combinations that could be curative for some. Right now, PARP inhibitors are fairly expensive but when they fall off their patent cliff, maybe usage could go from hundreds of thousands to millions of people.

In my view, the future of cancer will also increasingly involve early diagnosis. It’s intriguing to think that, for some patients, it might be possible to take olaparib or other drugs as a preventative treatment to wipe out rogue cells before they even get a chance to become a fully grown cancer.

What’s my advice for early career researchers? Take calculated risks. It’s a shots-on-goal thing: think about the approach, understand the biology, stay curious, and when things do not work out, try again and try something different.

Professor Sir Steve Jackson works at the Cancer Research UK Cambridge Institute. His work has been funded by Cancer Research UK, Wellcome, European Union, European Research Council, Worldwide Cancer Research, the Mark Foundation for Cancer Research and other organisations.

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Published:

With thanks to Jackie van Bochoven
Words: Louise Walsh
Photography: StillVision

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Academics and staff from the University of Cambridge are featured in the King’s Birthday Honours 2024, which recognises the achievements and service of people across the UK, from all walks of life.

Professor Tony Kouzarides, Professor of Cancer Biology, Senior Group Leader at the Gurdon Institute and Director and Co-Founder of the Milner Institute, has been awarded a Knighthood for his services to Healthcare Innovation and Delivery. Professor Kouzarides said: “I am delighted to receive this honour, which reinforces the importance of translating basic research into therapies by engaging academic researchers with healthcare businesses.”

Professor Barbara Sahakian, Professor of Clinical Neuropsychology in the Department of Psychiatry and a Fellow at Clare Hall, receives a CBE. Professor Sahakian, who is known for her research aimed at understanding the neural basis of cognitive, emotional and behavioural dysfunction in order to develop more effective pharmacological and psychological treatments, is honoured for her services to Research in Human Cognitive Processes. Professor Sahakian said: “I am delighted to receive this prestigious award, which recognises my research on human cognitive processes in health, psychiatric disorders and neurological diseases. I am grateful to my PhD students, postdoctoral fellows and colleagues for their collaboration.”

Professor Christine Holt, Professor of Developmental Neuroscience, receives a CBE for services to Neuroscience. Professor Holt said: “I’m surprised and thrilled to receive this honour. It’s a marvellous recognition of the research that has involved a whole team of talented, dedicated and inspiring colleagues over many years.”

Professor David Menon, founder of the Neurosciences Critical Care Unit (NCCU) at Addenbrooke’s Hospital, has been awarded a CBE. Professor Menon, who is noted for his national and global clinical and research leadership in traumatic brain injury, is honoured for his services to Neurocritical Care. He said: “I am deeply honoured to be nominated for a CBE and accept it on behalf of all those who have worked with me, during what has been – and continues to be – a very rewarding career.”

Professor Patrick Maxwell, Regius Professor of Physic and Head of School of Clinical Medicine, receives a CBE for services to Medical Research.

Professor Peter John Clarkson, Director of Cambridge Engineering Design Centre and Co-Director of Cambridge Public Health, receives a CBE. Professor Clarkson, who is known for his research in health and care improvement, inclusive design and systems design, is honoured for his services to Engineering and Design. Professor Clarkson said “I am delighted to receive this honour and thank all those extraordinary people I have had the pleasure to work with over the years who have supported me in so many interesting and transformative projects.”

Alexandra Bolton, Director of the Climate Governance Initiative, is awarded an OBE for services to the Built and Natural Environment. Alexandra said: “This wonderful and humbling recognition makes me in turn recognise the talented people who, throughout my career, have selflessly given me support, guidance and advice. I am enormously grateful for the honour, and for all those who have helped me along the way.”

Professor Anne-Christine Davis, Professor of Mathematical Physics, receives an OBE for services to Higher Education and to Scientific Research. Professor Davis said: “I am amazed and overwhelmed to receive this honour. I could not have done it alone and wish to thank my wonderful students and collaborators over the years. I would like to dedicate this honour to those women in STEMM who came before me and did not receive the recognition they deserved.”

Professor Shruti Kapila, Professor of History and Politics receives an OBE for services to Research in Humanities.

Details of University alumni who are recognised in the King’s Birthday Honours will be published on www.alumni.cam.ac.uk.

The University extends its congratulations to all academics, staff and alumni who have received an honour.

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Video footage of Iceland’s 2010 Eyjafjallajökull eruption is providing researchers from the University of Cambridge with rare, up-close observations of volcanic ash clouds — information that could help better forecast how far explosive eruptions disperse their hazardous ash particles.

When Eyjafjallajökull erupted in 2010, it ejected roughly 250 million tonnes of volcanic ash into the atmosphere: much of which was blown over Europe and into flight paths. With planes grounded, millions of air passengers were left stranded.

Forecasts of how ash will spread in the aftermath of an explosive eruption can help reduce impacts to aviation by informing decisions to shut down areas of airspace. But these forecasts require knowledge of what is happening at the volcano, information that often can’t be obtained directly and must instead be estimated.

In the new study, the researchers split a 17-minute film into time segments to understand how the Eyjafjallajökull ash cloud grew upwards and outwards as the eruption ensued.

“No one has previously observed the shape and speed of wind-blown ash clouds directly,” said Professor Andy Woods, lead author of the study from Cambridge’s Department of Earth Sciences and Institute for Energy and Environmental Flows. Their new video analysis method was reported in Nature Communications Earth and Environment.

By comparing characteristics of the ash cloud, such as its shape and speed, at time intervals through the video, the researchers were able to calculate the amount of ash spewed from the volcano.

That rate of ash flow, called eruption rate, is an important metric for forecasting ash cloud extent, said Woods. “The eruption rate determines how much ash goes up into the atmosphere, how high the ash cloud will go, how long the plume will stay buoyant, how quickly the ash will start falling to the ground and the area over which ash will land.”

Generally, the higher the ash plume, the wider the ash will be dispersed, and the smaller the ash particles are, the longer they stay buoyant. This dispersal can also depend on weather conditions, particularly the wind direction.

Volcanoes across the world are increasingly monitored via video, using webcams or high-resolution cameras. Woods thinks that, if high frame rate video observations can be accessed during an eruption, then this real-time information could be fed into ash cloud forecasts that more realistically reflect changing eruption conditions.

During the 17-minute footage of the Eyjafjallajökull eruption, the researchers observed that the eruption rate dropped by about half. “It’s amazing that you can learn eruption rate from a video, that’s something that we’ve previously only been able to calculate after an eruption has happened,” said Woods. “It’s important to know the changing eruption rate because that could impact the ash cloud dispersal downwind.”

It’s usually challenging for volcanologists to take continuous measurements of ash clouds whilst an eruption is happening. “Instead, much of our understanding of how ash clouds spread in the atmosphere is based on scaled-down lab models,” said Dr Nicola Mingotti, a researcher in Woods’ group and co-author of this study. These experiments are performed in water tanks, by releasing particle-laden or dyed saline solutions and analysing footage of the plume as it dissipates.

Woods and his collaborators have been running lab experiments like these for several years, most recently trying to understand how eruption plumes are dragged along by the wind. But it’s a big bonus to have video measurements from a real eruption, said Woods, and the real observations agree closely with what they’ve been observing in the lab. “Demonstrating our lab experiments are realistic is really important, both for making sure we understand how ash plumes work and that we forecast their movements effectively.”

Reference:
Mingotti, N., & Woods, A. W. (2024). Video-based measurements of the entrainment, speed and mass flux in a wind-blown eruption column. Communications Earth & Environment (2024). DOI: 10.1038/s43247-024-01402-x

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Study uncovers how the brain simulates possible future actions by drawing from our stored memories.

In pausing to think before making an important decision, we may imagine the potential outcomes of different choices we could make. While this ‘mental simulation’ is central to how we plan and make decisions in everyday life, how the brain works to accomplish this is not well understood. 

An international team of scientists has now uncovered neural mechanisms used in planning. Their results, published in the journal Nature Neuroscience, suggest that an interplay between the brain’s prefrontal cortex and hippocampus allows us to imagine future outcomes to guide our decisions.

“The prefrontal cortex acts as a ‘simulator,’ mentally testing out possible actions using a cognitive map stored in the hippocampus,” said co-author Marcelo Mattar from New York University. “This research sheds light on the neural and cognitive mechanisms of planning—a core component of human and animal intelligence. A deeper understanding of these brain mechanisms could ultimately improve the treatment of disorders affecting decision-making abilities.”

The roles of both the prefrontal cortex—used in planning and decision-making—and hippocampus—used in memory formation and storage—have long been established. However, their specific duties in deliberative decision-making, which are the types of decisions that require us to think before acting, are less clear.

To illuminate the neural mechanisms of planning, Mattar and his colleagues—Kristopher Jensen from University College London and Professor Guillaume Hennequin from Cambridge’s Department of Engineering —developed a computational model to predict brain activity during planning. They then analysed data from both humans and rats to confirm the validity of the model—a recurrent neural network (RNN), which learns patterns based on incoming information. 

The model took into account existing knowledge of planning and added new layers of complexity, including ‘imagined actions,’ thereby capturing how decision-making involves weighing the impact of potential choices—similar to how a chess player envisions sequences of moves before committing to one. These mental simulations of potential futures, modelled as interactions between the prefrontal cortex and hippocampus, enable us to rapidly adapt to new environments, such as taking a detour after finding a road is blocked.

The scientists validated this computational model using both behavioural and neural data. To assess the model’s ability to predict behaviour, the scientists conducted an experiment measuring how humans navigated an online maze on a computer screen and how long they had to think before each step.

To validate the model’s predictions about the role of the hippocampus in planning, they analysed neural recordings from rodents navigating a physical maze configured in the same way as in the human experiment. By giving a similar task to humans and rats, the researchers could draw parallels between the behavioural and neural data—an innovative aspect of this research.

“Allowing neural networks to decide for themselves when to ‘pause and think’ was a great idea, and it was surprising to see that in situations where humans spend time pondering what to do next, so do these neural networks,” said Hennequin. 

The experimental results were consistent with the computational model, showing an intricate interaction between the prefrontal cortex and hippocampus. In the human experiments, participants’ brain activity reflected more time thinking before acting in navigating the maze. In the experiments with laboratory rats, the animals’ neural responses in moving through the maze resembled the model’s simulations.

“Overall, this work provides foundational knowledge on how these brain circuits enable us to think before we act in order to make better decisions,” said Mattar. “In addition, a method in which both human and animal experimental participants and RNNs were all trained to perform the same task offers an innovative and foundational way to gain insights into behaviours.”

“This new framework will enable systematic studies of thinking at the neural level,” said Hennequin. “This will require a concerted effort from neurophysiologists and theorists, and I’m excited about the discoveries that lie ahead.” 

Reference:
Kristopher T. Jensen, Guillaume Hennequin & Marcelo G. Mattar. ‘A recurrent network model of planning explains hippocampal replay and human behavior.’ Nature Neuroscience (2024). DOI: 10.1038/s41593-024-01675-7

Adapted from an NYU press release.

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Astronomers have detected carbon in a galaxy just 350 million years after the Big Bang, the earliest detection of any element in the universe other than hydrogen.

Using the James Webb Space Telescope (JWST), an international team of astronomers led by the University of Cambridge observed a very young galaxy in the early universe and found that it contained surprising amounts of carbon, one of the seeds of life as we know it.

In astronomy, elements heavier than hydrogen or helium are classed as metals. The very early universe was almost entirely made up of hydrogen, the simplest of the elements, with small amounts of helium and tiny amounts of lithium.

Every other element that makes up the universe we observe today was formed inside a star. When stars explode as supernovas, the elements they produce are circulated throughout their host galaxy, seeding the next generation of stars. With every new generation of stars and ‘stardust’, more metals are formed, and after billions of years, the universe evolves to a point where it can support rocky planets like Earth and life like us.

The ability to trace the origin and evolution of metals will help us understand how we went from a universe made almost entirely of just two chemical elements, to the incredible complexity we see today.

“The very first stars are the holy grail of chemical evolution,” said lead author Dr Francesco D’Eugenio, from the Kavli Institute for Cosmology at Cambridge. “Since they are made only of primordial elements, they behave very differently to modern stars. By studying how and when the first metals formed inside stars, we can set a time frame for the earliest steps on the path that led to the formation of life.”

Carbon is a fundamental element in the evolution of the universe, since it can form into grains of dust that clump together, eventually forming into the first planetesimals and the earliest planets. Carbon is also key for the formation of life on Earth.

“Earlier research suggested that carbon started to form in large quantities relatively late – about one billion years after the Big Bang,” said co-author Professor Roberto Maiolino, also from the Kavli Institute. “But we’ve found that carbon formed much earlier – it might even be the oldest metal of all.”

The team used the JWST to observe a very distant galaxy – one of the most distant galaxies yet observed – just 350 million years after the Big Bang, more than 13 billion years ago. This galaxy is compact and low mass – about 100,000 times less massive than the Milky Way.

“It’s just an embryo of a galaxy when we observe it, but it could evolve into something quite big, about the size of the Milky Way,” said D’Eugenio. “But for such a young galaxy, it’s fairly massive.”

The researchers used Webb’s Near Infrared Spectrograph (NIRSpec) to break down the light coming from the young galaxy into a spectrum of colours. Different elements leave different chemical fingerprints in the galaxy’s spectrum, allowing the team to determine its chemical composition. Analysis of this spectrum showed a confident detection of carbon, and tentative detections of oxygen and neon, although further observations will be required to confirm the presence of these other elements.

“We were surprised to see carbon so early in the universe, since it was thought that the earliest stars produced much more oxygen than carbon,” said Maiolino. “We had thought that carbon was enriched much later, through entirely different processes, but the fact that it appears so early tells us that the very first stars may have operated very differently.” 

According to some models, when the earliest stars exploded as supernovas, they may have released less energy than initially expected. In this case, carbon, which was in the stars’ outer shell and was less gravitationally bound than oxygen, could have escaped more easily and spread throughout the galaxy, while a large amount of oxygen fell back and collapsed into a black hole.

“These observations tell us that carbon can be enriched quickly in the early universe,” said D’Eugenio. “And because carbon is fundamental to life as we know it, it’s not necessarily true that life must have evolved much later in the universe. Perhaps life emerged much earlier – although if there’s life elsewhere in the universe, it might have evolved very differently than it did here on Earth.”

The results have been accepted for publication in the journal Astronomy & Astrophysics and are based on data obtained within the JWST Advanced Deep Extragalactic Survey (JADES).

The research was supported in part by the European Research Council, the Royal Society, and the Science and Technology Facilities Council (STFC), part of UK Research and Innovation (UKRI).

Reference:
Francesco D’Eugenio et al. ‘JADES: Carbon enrichment 350 Myr after the Big Bang.’ Astronomy & Astrophysics (in press). DOI: 10.48550/arXiv.2311.09908

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Assumptions that tropical forest canopies protect from the effects of climate change are unfounded, say researchers.

A severe risk is that species are no longer able to survive within tropical forests as climate change intensifies, further exacerbating the global extinction crisis and degrading rainforest carbon stocks.David Edwards

Crucial strongholds for biodiversity are under threat as temperatures are rising in tropical forests, the world’s most diverse terrestrial ecosystems, a new study reveals.

It has been long assumed that the forest subcanopy and understorey – where direct sunlight is reduced – would be insulated from the worst climate change impacts by the shielding effect of the forest canopy.

A new study, published today in the journal Nature Climate Change, used a microclimate model to examine temperatures beneath the rainforest canopy across the global tropics.

This showed that between 2005 and 2019, most of the world’s undisturbed tropical forests experienced climate conditions at least partially outside the range of historic conditions. Many areas had transitioned to almost entirely new temperature averages.

Until recently, temperatures beneath the canopy in rainforests have remained relatively stable, meaning that the wildlife that lives there has evolved within a narrow range of temperatures. This leaves it poorly adapted to deal with temperatures outside this range.

The study found pronounced shifts in climate regimes in a significant proportion of tropical forests, including globally important national parks, indigenous reserves, and large tracts of ecologically unfragmented areas.

Recent studies in largely undisturbed, or primary lowland tropical forests have found changes in species composition and significant declines in animal, insect, and plant populations. These changes are attributed to warming temperatures and are consistent with the findings of the new research.

“Tropical forests are the true powerhouses of global biodiversity, and the complex networks of species they contain underpin vast carbon stocks that help to mitigate climate change. A severe risk is that species are no longer able to survive within tropical forests as climate change intensifies, further exacerbating the global extinction crisis and degrading rainforest carbon stocks,” said Professor David Edwards at the University of Cambridge’s Department of Plant Sciences, a study co-author.   

“Our study challenges the prevailing notion that tropical forest canopies will mitigate climate change impacts and it helps us understand how to prioritise conservation of these key areas of biodiversity effectively,” said Dr Alexander Lees, Reader in Biodiversity at Manchester Metropolitan University, a study co-author.

He added: “It is paramount that distant, wealth-related drivers of deforestation and degradation are addressed and that the future of those forests acting as climate refuges is secured by effecting legal protection, and by empowering indigenous communities.

“Notwithstanding the fundamental need for global carbon emission reductions, the prioritisation and protection of refugia and the restoration of highly threatened forests is vital to mitigate further damage to global tropical forest ecosystems.”

“Tropical forests, home to many of the world’s highly specialised species, are particularly sensitive to even small changes in climate,” said Dr Brittany Trew, Conservation Scientist for the Royal Society for the Protection of Birds, and lead author of the study.

She added: “Our research shows that climate change is already impacting vast areas of pristine tropical forest globally. To provide species with the best chance to adapt to these changes, these forests must be protected from additional human-induced threats.”

“The world’s rainforests are incredible reservoirs of biodiversity, harbouring species that live in micro-environments in which climate conditions are generally stable. Thus, they are particularly sensitive to any changes brought about by climate change. It is vital that we take measures to safeguard these ecosystems from human pressures,” said Ilya Maclean, Professor of Global Change Biology at the University of Exeter and senior author of the study.

The study was made possible through a global collaboration that included researchers at Mountains of the Moon University, Uganda; Universidade Federal do Pará, Brazil; the Brazilian Agricultural Research Corporation and Universidad Nacional de San Antonio Abad del Cusco, Perú. It was funded by the National Science Foundation (NSF).

Reference: Trew, B.T. et al: ‘Novel temperatures are already widespread beneath the world’s tropical forest canopies.’ Nature Climate Change, June 2024. DOI: 10.1038/s41558-024-02031-0

Adapted from a press released by Manchester Metropolitan University

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Two decades of cuckoo research have helped scientists to explain how battles between species can cause new species to arise

This exciting new finding could potentially apply to any pairs of species that are in battle with each other…the coevolutionary arms race could cause new species to emerge – and increase biodiversity on our planetRebecca Kilner

The theory of coevolution says that when closely interacting species drive evolutionary changes in each other this can lead to speciation – the evolution of new species. But until now, real-world evidence for this has been scarce.

Now a team of researchers has found evidence that coevolution is linked to speciation by studying the evolutionary arms race between cuckoos and the host birds they exploit.

Bronze-cuckoos lay their eggs in the nests of small songbirds. Soon after the cuckoo chick hatches, it pushes the host’s eggs out of the nest. The host not only loses all its own eggs, but spends several weeks rearing the cuckoo, which takes up valuable time when it could be breeding itself.

Each species of bronze-cuckoo closely matches the appearance of their host’s chicks, fooling the host parents into accepting the cuckoo.

The study shows how these interactions can cause new species to arise when a cuckoo species exploits several different hosts. If chicks of each host species have a distinct appearance, and hosts reject odd-looking nestlings, then the cuckoo species diverges into separate genetic lineages, each mimicking the chicks of its favoured host. These new lineages are the first sign of new species emerging.

The study is published today in the journal Science.

“This exciting new finding could potentially apply to any pairs of species that are in battle with each other. Just as we’ve seen with the cuckoo, the coevolutionary arms race could cause new species to emerge – and increase biodiversity on our planet,” said Professor Kilner in the University of Cambridge’s Department of Zoology, a co-author of the report.

The striking differences between the chicks of different bronze-cuckoo lineages correspond to subtle differences in the plumage and calls of the adults, which help males and females that specialise on the same host to recognise and pair with each other.

“Cuckoos are very costly to their hosts, so hosts have evolved the ability to recognise and eject cuckoo chicks from their nests,’’ said Professor Naomi Langmore at the Australian National University, Canberra, lead author of the study. 

She added: “Only the cuckoos that most resemble the host’s own chicks have any chance of escaping detection, so over many generations the cuckoo chicks have evolved to mimic the host chicks.”

The study revealed that coevolution is most likely to drive speciation when the cuckoos are very costly to their hosts, leading to a ‘coevolutionary arms race’ between host defences and cuckoo counter-adaptations.

A broad scale analysis across all cuckoo species found that those lineages that are most costly to their hosts have higher speciation rates than less costly cuckoo species and their non-parasitic relatives.

“This finding is significant in evolutionary biology, showing that coevolution between interacting species increases biodiversity by driving speciation,” said Dr Clare Holleley at the Australian National Wildlife Collection within CSIRO, Canberra, senior author of the report.

The study was made possible by the team’s breakthrough in extracting DNA from eggshells in historical collections, and sequencing it for genetic studies.

The researchers were then able to combine two decades of behavioural fieldwork with DNA analysis of specimens of eggs and birds held in museums and collections.

The study involved an international team of researchers at the University of Cambridge, Australian National University, CSIRO (Australia’s national science agency), and the University of Melbourne. It was funded by the Australian Research Council.

Reference: Langmore, N.E. et al: ‘Coevolution with hosts underpins speciation in brood-parasitic cuckoos.’ Science, May 2024. DOI: 10.1126/science.adj3210

Adapted from a press release by the Australian National University.

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The two earliest and most distant galaxies yet confirmed, dating back to only 300 million years after the Big Bang, have been discovered using NASA’s James Webb Space Telescope (JWST), an international team of astronomers today announced.

These galaxies join a small but growing population of galaxies from the first half billion years of cosmic history where we can really probe the stellar populations and the distinctive patterns of chemical elements within themFrancesco D’Eugenio

Found in a region near the Hubble Ultra Deep Field by the JWST Advanced Deep Extragalactic Survey (JADES) team, these galaxies mark a major milestone in the study of the early Universe.

“These galaxies join a small but growing population of galaxies from the first half billion years of cosmic history where we can really probe the stellar populations and the distinctive patterns of chemical elements within them,” said Dr Francesco D’Eugenio of the Kavli Institute for Cosmology at the University of Cambridge, one of the team behind the discovery.

Because of the expansion of the Universe, the light from distant galaxies stretches to longer wavelength as it travels, an effect known as redshift. In these galaxies, the effect is extreme, stretching by a factor of 15, and moving even the ultraviolet light of the galaxies to infrared wavelengths where only JWST has the capability to see it.

Modern theory holds that galaxies develop in special regions where gravity has concentrated the cosmic gas and dark matter into dense lumps known as ‘halos’. These halos evolved quickly in the early Universe, rapidly merging into more and more massive collections of matter. This fast development is why astronomers are so eager to find yet earlier galaxies: each small increment moves our eyes to a less developed period, where luminous galaxies are even more distinctive and unusual.

The two newly discovered galaxies have been confirmed spectroscopically. In keeping with the collaboration’s standard naming practice, the galaxies are now known as JADES-GS-z14-0 and JADES-GS-z14-1, the former being the more distant of the two.

In addition to being the new distance record holder, JADES-GS-z14-0 is remarkable for how big and bright it is. JWST measures the galaxy at over 1,600 light-years in diameter. Many of the most luminous galaxies produce the bulk of their light via gas falling into a supermassive black hole, producing a quasar, but at this size JADES-GS-z14-0 cannot be this. Instead, the researchers believe the light is being produced by young stars.

The combination of the high luminosity and the stellar origin makes JADES-GS-z14-0 the most distinctive evidence yet found for the rapid formation of large, massive galaxies in the early Universe. This trend runs counter to the pre-JWST expectations of theories of galaxy formation. Evidence for surprisingly vigorous early galaxies appeared even in the first JWST images and has been mounting in the first two years of the mission.

“JADES-GS-z14-0 now becomes the archetype of this phenomenon,” said Dr Stefano Carniani of the Scuola Normale Superiore in Pisa, lead author on the discovery paper. “It is stunning that the Universe can make such a galaxy in only 300 million years.”

Despite its luminosity, JADES-GS-z14-0 was a puzzle for the JADES team when they first spotted it over a year ago, as it appears close enough on the sky to a foreground galaxy that the team couldn’t be sure that the two weren’t neighbours. But in October 2023, the JADES team conducted even deeper imaging—five full days with the JWST Near-Infrared Camera on just one field—to form the “JADES Origins Field.” With the use of filters designed to better isolate the earliest galaxies, confidence grew that JADES-GS-z14-0 was indeed very distant.

“We just couldn’t see any plausible way to explain this galaxy as being merely a neighbour of the more nearby galaxy,” said Dr Kevin Hainline, research professor at the University of Arizona.

Fortunately, the galaxy happened to fall in a region where the team had conducted ultra-deep imaging with the JWST Mid-Infrared Instrument. The galaxy was bright enough to be detected in 7.7 micron light, with a higher intensity than extrapolation from lower wavelengths would predict.

“We are seeing extra emission from hydrogen and possibly even oxygen atoms, as is common in star-forming galaxies, but here shifted out to an unprecedented wavelength,” said Jakob Helton, graduate student at the University of Arizona and lead author of a second paper on this finding.

These combined imaging results convinced the team to include the galaxy in what was planned to be the capstone observation of JADES, a 75-hour campaign to conduct spectroscopy on faint early galaxies. The spectroscopy confirmed their hopes that JADES-GS-z14-0 was indeed a record-breaking galaxy and that the fainter candidate, JADES-GS-z14-1, was nearly as far away.

Beyond the confirmation of distance, the spectroscopy allows further insight into the properties of the two galaxies. Being comparatively bright, JADES-GS-z14-0 will permit detailed study.

“We could have detected this galaxy even if it were 10 times fainter, which means that we could see other examples yet earlier in the Universe—probably into the first 200 million years,” says Brant Robertson, professor of astronomy and astrophysics at the University of California-Santa Cruz, and lead author of a third paper on the team’s study of the evolution of this early population of galaxies. “The early Universe has so much more to offer.”

Reference
Carniani, S et al. A shining cosmic dawn: spectroscopic confirmation of two luminous galaxies at z∼14. arXiv:2405.18485 [astro-ph.GA]

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Clare Hall, Cambridge and LUT University, Finland, establish a Visiting Fellowship programme and joint Global Prize for Solutions to Climate Change Threats. Please read more about this story here

We very much look forward to welcoming high-flying academics from LUT over the years to come to our unique interdisciplinary research communityClare Hall President Alan Short

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The University of Cambridge has received £5 million funding from the British Heart Foundation (BHF) to support its world-class cardiovascular disease research over the next five years, the charity has announced.

This is a fantastic achievement from the whole Cambridge team. This award will support our multiple research programmes.Martin Bennett

The funding will support the university to cultivate a world-class research environment that encourages collaboration, inclusion and innovation, and where visionary scientists can drive lifesaving breakthroughs.

Professor Martin Bennett, BHF Professor of Cardiovascular Sciences at the University of Cambridge, said: “This is a fantastic achievement from the whole Cambridge team. This award will support our multiple research programmes identifying new targets and treatments for vascular disease and heart failure, new ways to reduce the consequences of diabetes and obesity, and how we can get our research used to treat patients.”

The Cambridge award is part of a £35 million boost to UK cardiovascular disease research from the British Heart Foundation. It comes from the charity’s highly competitive Research Excellence Awards funding scheme. The £5 million award to the University of Cambridge will support researchers to:

• Combine their expertise to work on cardiovascular diseases and in populations with high unmet need.
• Identify new markers and disease targets for a wide range of cardiovascular diseases, and test new drugs in clinical trials.
• Develop new ways to diagnose cardiovascular disease and harness the power of artificial intelligence from imaging and health records to identify people at highest risk.
• Generate user-friendly risk communication and management tools to improve the prevention and management of cardiovascular disease.

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “We’re delighted to continue to support research at the University of Cambridge addressing the biggest challenges in cardiovascular disease. This funding recognises the incredible research happening at Cambridge and will help to further its reputation as a global leader in the field.

“With generous donations from our supporters, this funding will attract the brightest talent, power cutting-edge science, and unlock lifesaving discoveries that can turn the tide on the devastation caused by heart and circulatory diseases.”

Research Excellence Awards offer greater flexibility than traditional research funding, allowing scientists to quickly launch ambitious projects that can act as a springboard for larger, transformative funding applications.

The funding also aims to break down the silos that have traditionally existed in research, encouraging collaboration between experts from diverse fields. From clinicians to data scientists, biologists to engineers, the funding will support universities to attract the brightest minds, nurture new talent and foster collaboration to answer the biggest questions in heart and circulatory disease research.

The University of Cambridge has previously been awarded £9 million funding through the BHF’s Research Excellence Awards scheme. This funding has supported research that will lay the foundations for future breakthroughs, including:

• Research showing that low doses of a cancer drug could improve recovery after a heart attack. The drug boosts activity of anti-inflammatory immune cells that can cause harmful inflammation in blood vessels supplying the heart. It’s currently being tested in clinical trials to see if it benefits patients.
• A new risk calculator to enable doctors across the UK and Europe predict who is at risk of having a heart attack or stroke in the next 10 years with greater accuracy. The calculator has been adopted by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice.
• Developing imaging and artificial intelligence tools to improve diagnosis of heart and vascular disease by enhancing analysis of scans for disease activity and high-risk fatty plaques. These tools can be rapidly implemented to support diagnosis, treatment and prevention.
• A study investigating whether an epilepsy medication could help to prevent strokes in people with a common gene variant. The change in the gene HDAC9 can cause it to become ‘overactive’ and increase stroke risk. The epilepsy medication sodium valproate blocks the HDAC9 activity, so could reduce stroke risk in people with the variant.
• Discovery of rare and common changes in the genetic code that influences proteins and small molecules in the blood, helping us understand the development of cardiovascular diseases and identify novel drug targets.

Adapted from a press release by BHF

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3D reconstructions suggest that simple marine animals living over 560 million years ago drove the emergence of more complex life by mixing the seawater around them

It’s exciting to learn that the very first animals from 580 million years ago had a significant impact on their environment, despite not being able to move or swim.Emily Mitchell

A study involving the University of Cambridge has used virtual recreations of the earliest animal ecosystems, known as marine animal forests, to demonstrate the part they played in the evolution of our planet.

Using state-of-the-art computer simulations of fossils from the Ediacaran time period – approximately 565 million years ago – scientists discovered how these animals mixed the surrounding seawater. This may have affected the distribution of important resources such as food particles and could have increased local oxygen levels.

Through this process, the scientists think these early communities could have played a crucial role in shaping the initial emergence of large and complex organisms prior to a major evolutionary radiation of different forms of animal life, the so-called Cambrian ‘explosion’.

Over long periods of time, these changes might have allowed life forms to perform more complicated functions, like those associated with the evolution of new feeding and movement styles.

The study was led by the Natural History Museum and is published today in the journal Current Biology.

Dr Emily Mitchell at the University of Cambridge’s Department of Zoology, a co-author of the report, said: “It’s exciting to learn that the very first animals from 580 million years ago had a significant impact on their environment, despite not being able to move or swim. We’ve found they mixed up the water and enabled resources to spread more widely – potentially encouraging more evolution.”

Scientists know from modern marine environments that nutrients like food and oxygen are carried in seawater, and that animals can affect water flow in ways that influence the distribution of these resources.

To test how far back this process goes in Earth’s history, the team looked at some of the earliest examples of marine animal communities, known from rocks at Mistaken Point, Newfoundland, Canada. This world-famous fossil site perfectly preserves early life forms thanks to a cover of volcanic ash (sometimes referred to as an ‘Ediacaran Pompeii’).

Although some of these life forms look like plants, analysis of their anatomy and growth strongly suggests they are animals. Owing to the exceptional preservation of the fossils, the scientists could recreate digital models of key species, which were used as a basis for further computational analyses.

First author Dr Susana Gutarra, a Scientific Associate at the Natural History Museum, said: “We used ecological modelling and computer simulations to investigate how 3D virtual assemblages of Ediacaran life forms affected water flow. Our results showed that these communities were capable of ecological functions similar to those seen in present-day marine ecosystems.”

The study showed that one of the most important Ediacaran organisms for disrupting the flow of water was the cabbage-shaped animal Bradgatia, named after Bradgate Park in England. The Bradgatia from Mistaken Point are among some of the largest fossils known from this site, reaching diameters of over 50 centimetres.

Through their influence on the water around them, the scientists believe these Ediacaran organisms might have been capable of enhancing local oxygen concentrations. This biological mixing might also have had repercussions for the wider environment, possibly making other areas of the sea floor more habitable and perhaps even driving evolutionary innovation.

Dr Imran Rahman, lead author and Principal Researcher at the Natural History Museum, said: “The approach we’ve developed to study Ediacaran fossil communities is entirely new in palaeontology, providing us with a powerful tool for studying how past and present marine ecosystems might shape and influence their environment.”

The research was funded by the UK Natural Environment Research Council and the US National Science Foundation.

Reference: Gutarra-Diaz, S.“Ediacaran marine animal forests and the ventilation of the oceans.” May 2024, Current Biology. DOI: 10.1016/j.cub.2024.04.059

Adapted from a press release by the Natural History Museum

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An international team of astronomers, led by the University of Cambridge, has used the James Webb Space Telescope to find evidence for an ongoing merger of two galaxies and their massive black holes when the Universe was only 740 million years old. This marks the most distant detection of a black hole merger ever obtained and the first time that this phenomenon has been detected so early in the Universe.

Massive black holes have been shaping the evolution of galaxies from the very beginningHannah Übler

Astronomers have found supermassive black holes with masses of millions to billions times that of the Sun in most massive galaxies in the local Universe, including in our Milky Way galaxy. These black holes have likely had a major impact on the evolution of the galaxies they reside in. However, scientists still don’t fully understand how these objects grew to become so massive.

The finding of gargantuan black holes already in place in the first billion years after the Big Bang indicates that such growth must have happened very rapidly, and very early. Now, the James Webb Space Telescope is shedding new light on the growth of black holes in the early Universe.

The new Webb observations have provided evidence for an ongoing merger of two galaxies and their massive black holes when the Universe was just 740 million years old. The system is known as ZS7.

Massive black holes that are actively accreting matter have distinctive spectrographic features that allow astronomers to identify them. For very distant galaxies, like those in this study, these signatures are inaccessible from the ground and can only be seen with Webb.

“We found evidence for very dense gas with fast motions in the vicinity of the black hole, as well as hot and highly ionised gas illuminated by the energetic radiation typically produced by black holes in their accretion episodes,” said lead author Dr Hannah Übler of Cambridge’s Cavendish Laboratory and Kavli Institute for Cosmology. “Thanks to the unprecedented sharpness of its imaging capabilities, Webb also allowed our team to spatially separate the two black holes.”

The team found that one of the two black holes has a mass that is 50 million times the mass of the Sun. “The mass of the other black hole is likely similar, although it is much harder to measure because this second black hole is buried in dense gas,” said team member Professor Roberto Maiolino, also from the Kavli Institute.

“Our findings suggest that merging is an important route through which black holes can rapidly grow, even at cosmic dawn,” said Übler. “Together with other Webb findings of active, massive black holes in the distant Universe, our results also show that massive black holes have been shaping the evolution of galaxies from the very beginning.”

The team notes that once the two black holes merge, they will also generate gravitational waves. Events like this will be detectable with the next generation of gravitational wave observatories, such as the upcoming Laser Interferometer Space Antenna (LISA) mission, which was recently approved by the European Space Agency and will be the first space-based observatory dedicated to studying gravitational waves.

This discovery was from observations made as part of the Galaxy Assembly with NIRSpec Integral Field Spectroscopy programme. The team has recently been awarded a new Large Programme in Webb’s Cycle 3 of observations, to study in detail the relationship between massive black holes and their host galaxies in the first billion years. An important component of this programme will be to systematically search for and characterise black hole mergers. This effort will determine the rate at which black hole merging occurs at early cosmic epochs and will assess the role of merging in the early growth of black holes and the rate at which gravitational waves are produced from the dawn of time.

These results have been published in the Monthly Notices of the Royal Astronomical Society.

Reference:
Hannah Übler et al. ‘GA-NIFS: JWST discovers an offset AGN 740 million years after the big bang’ Monthly Notices of the Royal Astronomical Society (2024). DOI: 10.1093/mnras/stae943

Adapted from a press release by the European Space Agency.

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Ten outstanding Cambridge researchers have been elected as Fellows of the Royal Society, the UK’s national academy of sciences and the oldest science academy in continuous existence.

The Royal Society is a self-governing Fellowship of many of the world’s most distinguished scientists drawn from all areas of science, engineering and medicine.

The Society’s fundamental purpose, as it has been since its foundation in 1660, is to recognise, promote and support excellence in science and to encourage the development and use of science for the benefit of humanity.

This year, over 90 researchers, innovators and communicators from around the world have been elected as Fellows of the Royal Society for their substantial contribution to the advancement of science. Nine of these are from the University of Cambridge.

Sir Adrian Smith, President of the Royal Society said: “I am pleased to welcome such an outstanding group into the Fellowship of the Royal Society.

“This new cohort have already made significant contributions to our understanding of the world around us and continue to push the boundaries of possibility in academic research and industry.

“From visualising the sharp rise in global temperatures since the industrial revolution to leading the response to the Covid-19 pandemic, their diverse range of expertise is furthering human understanding and helping to address some of our greatest challenges. It is an honour to have them join the Fellowship.”

The Fellows and Foreign Members join the ranks of Stephen Hawking, Isaac Newton, Charles Darwin, Albert Einstein, Lise Meitner, Subrahmanyan Chandrasekhar and Dorothy Hodgkin.

The new Cambridge fellows are: 
 

Professor Sir John Aston Kt FRS

Aston is the Harding Professor of Statistics in Public Life at the Statistical Laboratory, Department of Pure Mathematics and Mathematical Statistics, where he develops techniques for public policy and improves the use of quantitative methods in public policy debates.

From 2017 to 2020 he was the Chief Scientific Adviser to the Home Office, providing statistical and scientific advice to ministers and officials, and was involved in the UK’s response to the Covid pandemic. He was knighted in 2021 for services to statistics and public policymaking, and is a Fellow of Churchill College.
 

Professor Sarah-Jayne Blakemore FBA FMedSci FRS

Blakemore is the Professor of Psychology and Cognitive Neuroscience, Department of Psychology, and leader of the Developmental Cognitive Neuroscience Group. Her research focuses on the development of social cognition and decision making in the human adolescent brain, and adolescent mental health. 

Blakemore has been awarded several national and international prizes for her research, and is a Fellow of the British Academy, the American Association of Psychological Science and the Academy of Medical Sciences. 
 

Professor Patrick Chinnery FMedSci FRS

Chinnery is Professor of Neurology and head of the University’s Department of Clinical Neurosciences, and a Fellow of Gonville & Caius College. He was appointed Executive Chair of the Medical Research Council last year, having previously been MRC Clinical Director since 2019.

His principal research is the role of mitochondria in human disease and developing new treatments for mitochondrial disorders. Chinnery is a Wellcome Principal Research Fellow with a lab based in the MRC Mitochondrial Biology Unit and jointly chairs the NIHR BioResource for Translational Research in Common and Rare Diseases. He is a Fellow of the Academy of Medical Sciences.

Professor Rebecca Fitzgerald OBE FMedSci FRS

Fitzgerald is Professor of Cancer Prevention in the Department of Oncology and the inaugural Director of the University’s new Early Cancer Institute, which launched in 2022. She is a Fellow of Trinity College.

Her pioneering work to devise a first-in-class, non-endoscopic capsule sponge test for identifying individuals at high risk for oesophageal cancer has won numerous prizes, including the Westminster Medal, and this test is now being rolled out in the NHS and beyond by her spin-out Cyted Ltd.

Professor David Hodell FRS

Hodell is the Woodwardian Professor of Geology and Director of the Godwin Laboratory for Palaeoclimate Research in the Department of Earth Sciences, and a Fellow of Clare College.

A marine geologist and paleoclimatologist, his research focuses on high-resolution paleoclimate records from marine and lake sediments, as well as mineral deposits, to better understand past climate dynamics. Hodell is a fellow of the American Geophysical Union and the American Association for the Advancement of Science. He has received the Milutin Milankovic Medal.

Professor Eric Lauga FRS

Lauga is Professor of Applied Mathematics in the Department of Applied Mathematics and Theoretical Physics, where his research is in fluid mechanics, biophysics and soft matter. Lauga is the author, or co-author, of over 180 publications and currently serves as Associate Editor for the journal Physical Review Fluids.

He is a recipient of three awards from the American Physical Society: the Andreas Acrivos Dissertation Award in Fluid Dynamics, the François Frenkiel Award for Fluid Mechanics and the Early Career Award for Soft Matter Research. He is a Fellow of the American Physical Society and of Trinity College.

Professor George Malliaras FRS

Malliaras is the Prince Philip Professor of Technology in the Department of Engineering, where he leads a group that works on the development and translation of implantable and wearable devices that interface with electrically active tissues, with applications in neurological disorders and brain cancer.

Research conducted by Malliaras has received awards from the European Academy of Sciences, the New York Academy of Sciences, and the US National Science Foundation among others. He is a Fellow of the Materials Research Society and of the Royal Society of Chemistry.
 

Professor Lloyd Peck FRI FRSB FRS

Peck is a marine biologist at the British Antarctic Survey and a fellow at Wolfson College, Cambridge.

He identified oxygen as a factor in polar gigantism and identified problems with protein synthesis as the cause of slow development and growth in polar marine species. He was awareded a Polar Medal in 2009, the PLYMSEF Silver medal in 2015 and an Erskine Fellowship at the University of Canterbury, Christchurch in 2016-2017. 

Professor Oscar Randal-Williams FRS

Randal-Williams is the Sadleirian Professor of Pure Mathematics in the Department of Pure Mathematics and Mathematical Statistics.

He has received the Whitehead Prize from the London Mathematical Society, a Philip Leverhulme Prize, the Oberwolfach Prize, the Dannie Heineman Prize of the Göttingen Academy of Sciences and Humanities, and was jointly awarded the Clay Research Award.

Randal-Williams is one of two managing editors of the Proceedings of the London Mathematical Society, and an editor of the Journal of Topology.

Professor Mihaela van der Schaar FRS

Van der Schaar is the John Humphrey Plummer Professor of Machine Learning, Artificial Intelligence and Medicine in the Departments of Applied Mathematics and Theoretical Physics, Engineering and Medicine.

She is the founder and director of the Cambridge Centre for AI in Medicine, and a Fellow at The Alan Turing Institute. Her work has received numerous awards, including the Oon Prize on Preventative Medicine, a National Science Foundation CAREER Award, and the IEEE Darlington Award.

Van der Schaar is credited as inventor on 35 US patents, and has made over 45 contributions to international standards for which she received three ISO Awards. In 2019, a Nesta report declared her the most-cited female AI researcher in the UK.


 

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The college is sad to announce that our Bye-Fellow Jack Lang died on Tuesday 23 April after a long illness.

Jack matriculated in 1966 and had been, at various times, our Director of Studies in Computer Science and in Management Studies. He was appointed a Bye-Fellow in 2003.

Jack was a serial entrepreneur and business angel. Interested in ‘computer science and how the brain works’, his undergraduate degree in Mechanical Sciences led to a Computer Science diploma and a spell as Demonstrator in the Computer Laboratory. He left the University to found, with Professor Shon Ffowcs-Williams, the consulting company TopExpress, one of whose projects was designing some of the software for the BBC Microcomputer.

Jack also founded Electronic Share Information Ltd, which was acquired by E*Trade Inc in 1995, and was a founder of Netchannel Ltd, which was acquired in 1998 by ntl, for whom he subsequently became Chief Technologist. He was also co-founder of Raspberry Pi in 2012, which achieved its aim of putting high-performance, low-cost, general-purpose computing platforms in the hands of enthusiasts and engineers all over the world. Over 60 million computers have been sold in the last decade and the Raspberry Pi Foundation enables young people to realise their full potential through the power of computing and digital technologies. Jack  was one of the most significant figures in computing education in the UK.

He was author of ‘The High Tech Entrepreneurs Handbook’ (2002) and taught courses in Business Studies, Entrepreneurship and Ecommerce for the University of Cambridge Computer Science Laboratory. He was Entrepreneur in Residence at the Centre for Entrepreneurial Learning at the Judge Business School.

Jack was a keen sourdough baker, a passionate cook and a caring owner of a very productive apple orchard. A side project was as founder (and sometime chef) of Midsummer House Restaurant, Cambridge’s only Michelin starred restaurant. And in keeping with his polymath nature, having mastered the art of designing and making fireworks at a relatively young age, he also became the architect of, and long-term champion for, the Cambridge fireworks display.

He will be much missed and long remembered by many around the world.

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Researchers have developed tiny, flexible devices that can wrap around individual nerve fibres without damaging them.

The ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatmentsGeorge Malliaras

The researchers, from the University of Cambridge, combined flexible electronics and soft robotics techniques to develop the devices, which could be used for the diagnosis and treatment of a range of disorders, including epilepsy and chronic pain, or the control of prosthetic limbs.

Current tools for interfacing with the peripheral nerves – the 43 pairs of motor and sensory nerves that connect the brain and the spinal cord – are outdated, bulky and carry a high risk of nerve injury. However, the robotic nerve ‘cuffs’ developed by the Cambridge team are sensitive enough to grasp or wrap around delicate nerve fibres without causing any damage.

Tests of the nerve cuffs in rats showed that the devices only require tiny voltages to change shape in a controlled way, forming a self-closing loop around nerves without the need for surgical sutures or glues.

The researchers say the combination of soft electrical actuators with neurotechnology could be an answer to minimally invasive monitoring and treatment for a range of neurological conditions. The results are reported in the journal Nature Materials.

Electric nerve implants can be used to either stimulate or block signals in target nerves. For example, they might help relieve pain by blocking pain signals, or they could be used to restore movement in paralysed limbs by sending electrical signals to the nerves. Nerve monitoring is also standard surgical procedure when operating in areas of the body containing a high concentration of nerve fibres, such as anywhere near the spinal cord.

These implants allow direct access to nerve fibres, but they come with certain risks. “Nerve implants come with a high risk of nerve injury,” said Professor George Malliaras from Cambridge’s Department of Engineering, who led the research. “Nerves are small and highly delicate, so anytime you put something large, like an electrode, in contact with them, it represents a danger to the nerves.”

“Nerve cuffs that wrap around nerves are the least invasive implants currently available, but despite this they are still too bulky, stiff and difficult to implant, requiring significant handling and potential trauma to the nerve,” said co-author Dr Damiano Barone from Cambridge’s Department of Clinical Neurosciences.

The researchers designed a new type of nerve cuff made from conducting polymers, normally used in soft robotics. The ultra-thin cuffs are engineered in two separate layers. Applying tiny amounts of electricity – just a few hundred millivolts – causes the devices to swell or shrink.

The cuffs are small enough that they could be rolled up into a needle and injected near the target nerve. When activated electrically, the cuffs will change their shape to wrap around the nerve, allowing nerve activity to be monitored or altered.

“To ensure the safe use of these devices inside the body, we have managed to reduce the voltage required for actuation to very low values,” said Dr Chaoqun Dong, the paper’s first author. “What’s even more significant is that these cuffs can change shape in both directions and be reprogrammed. This means surgeons can adjust how tightly the device fits around a nerve until they get the best results for recording and stimulating the nerve.”

Tests in rats showed that the cuffs could be successfully placed without surgery, and formed a self-closing loop around the target nerve. The researchers are planning further testing of the devices in animal models, and are hoping to begin testing in humans within the next few years.

“Using this approach, we can reach nerves that are difficult to reach through open surgery, such as the nerves that control, pain, vision or hearing, but without the need to implant anything inside the brain,” said Barone. “The ability to place these cuffs so they wrap around the nerves makes this a much easier procedure for surgeons, and it’s less risky for patients.”

“The ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments,” said Malliaras. “In future, we might be able to have implants that can move through the body, or even into the brain – it makes you dream how we could use technology to benefit patients in future.”

The research was supported in part by the Swiss National Science Foundation, the Cambridge Trust, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

Reference:
Chaoqun Dong et al. ‘Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.’ Nature Materials (2024). DOI: 10.1038/s41563-024-01886-0

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Machines can learn not only to make predictions, but to handle causal relationships. An international research team shows how this could make medical treatments safer, more efficient, and more personalised.

Artificial intelligence techniques can be helpful for multiple medical applications, such as radiology or oncology, where the ability to recognise patterns in large volumes of data is vital. For these types of applications, the AI compares information against learned examples, draws conclusions, and makes extrapolations.

Now, an international team led by researchers from Ludwig-Maximilians-Universität München (LMU) and including researchers from the University of Cambridge, is exploring the potential of a comparatively new branch of AI for diagnostics and therapy.

The researchers found that causal machine learning (ML) can estimate treatment outcomes – and do so better than the machine learning methods generally used to date. Causal machine learning makes it easier for clinicians to personalise treatment strategies, which individually improves the health of patients.

The results, reported in the journal Nature Medicine, suggest how causal machine learning could improve the effectiveness and safety of a variety of medical treatments.

Classical machine learning recognises patterns and discovers correlations. However, the principle of cause and effect remains closed to machines as a rule; they cannot address the question of why. When making therapy decisions for a patient, the ‘why’ is vital to achieve the best outcomes.

“Developing machine learning tools to address why and what if questions is empowering for clinicians, because it can strengthen their decision-making processes,” said senior author Professor Mihaela van der Schaar, Director of the Cambridge Centre for AI in Medicine. “But this sort of machine learning is far more complex than assessing personalised risk.”

For example, when attempting to determine therapy decisions for someone at risk of developing diabetes, classical ML would aim to predict how probable it is for a given patient with a range of risk factors to develop the disease. With causal ML, it would be possible to answer how the risk changes if the patient receives an anti-diabetes drug; that is, gauge the effect of a cause. It would also be possible to estimate whether metformin, the commonly-prescribed medication, would be the best treatment, or whether another treatment plan would be better.

To be able to estimate the effect of a hypothetical treatment, the AI models must learn to answer ‘what if?’ questions. “We give the machine rules for recognising the causal structure and correctly formalising the problem,” said Professor Stefan Feuerriegel from LMU, who led the research. “Then the machine has to learn to recognise the effects of interventions and understand, so to speak, how real-life consequences are mirrored in the data that has been fed into the computers.”

Even in situations for which reliable treatment standards do not yet exist or where randomised studies are not possible for ethical reasons because they always contain a placebo group, machines could still gauge potential treatment outcomes from the available patient data and form hypotheses for possible treatment plans, so the researchers hope.

With such real-world data, it should generally be possible to describe the patient cohorts with ever greater precision in the estimates, bringing individualised therapy decisions that much closer. Naturally, there would still be the challenge of ensuring the reliability and robustness of the methods.

“The software we need for causal ML methods in medicine doesn’t exist out of the box,” says Feuerriegel. “Rather, complex modelling of the respective problem is required, involving close collaboration between AI experts and doctors.”

In other fields, such as marketing, explains Feuerriegel, the work with causal ML has already been in the testing phase for some years now. “Our goal is to bring the methods a step closer to practice,” he said. The paper describes the direction in which things could move over the coming years.”

“I have worked in this area for almost 10 years, working relentlessly in our lab with generations of students to crack this problem,” said van der Schaar, who is affiliated with the Departments of Applied Mathematics and Theoretical Physics, Engineering and Medicine. “It’s an extremely challenging area of machine learning, and seeing it come closer to clinical use, where it will empower clinicians and patients alike, is very satisfying.”

Van der Schaar is continuing to work closely with clinicians to validate these tools in diverse clinical settings, including transplantation, cancer and cardiovascular disease.

Reference:
Stefan Feuerriegel et al. ‘Causal machine learning for predicting treatments.’ Nature Medicine (2024). DOI: 10.1038/s41591-024-02902-1

Adapted from an LMU media release.

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The energy density of supercapacitors – battery-like devices that can charge in seconds or a few minutes – can be improved by increasing the ‘messiness’ of their internal structure.

This could be a turning point for a field that’s been stuck for a little while.Alex Forse

Researchers led by the University of Cambridge used experimental and computer modelling techniques to study the porous carbon electrodes used in supercapacitors. They found that electrodes with a more disordered chemical structure stored far more energy than electrodes with a highly ordered structure.

Supercapacitors are a key technology for the energy transition and could be useful for certain forms of public transport, as well as for managing intermittent solar and wind energy generation, but their adoption has been limited by poor energy density.

The researchers say their results, reported in the journal Science, represent a breakthrough in the field and could reinvigorate the development of this important net-zero technology.

Like batteries, supercapacitors store energy, but supercapacitors can charge in seconds or a few minutes, while batteries take much longer. Supercapacitors are far more durable than batteries, and can last for millions of charge cycles. However, the low energy density of supercapacitors makes them unsuitable for delivering long-term energy storage or continuous power.

“Supercapacitors are a complementary technology to batteries, rather than a replacement,” said Dr Alex Forse from Cambridge’s Yusuf Hamied Department of Chemistry, who led the research. “Their durability and extremely fast charging capabilities make them useful for a wide range of applications.”

A bus, train or metro powered by supercapacitors, for example, could fully charge in the time it takes to let passengers off and on, providing it with enough power to reach the next stop. This would eliminate the need to install any charging infrastructure along the line. However, before supercapacitors are put into widespread use, their energy storage capacity needs to be improved.

While a battery uses chemical reactions to store and release charge, a supercapacitor relies on the movement of charged molecules between porous carbon electrodes, which have a highly disordered structure. “Think of a sheet of graphene, which has a highly ordered chemical structure,” said Forse. “If you scrunch up that sheet of graphene into a ball, you have a disordered mess, which is sort of like the electrode in a supercapacitor.”

Because of the inherent messiness of the electrodes, it’s been difficult for scientists to study them and determine which parameters are the most important when attempting to improve performance. This lack of clear consensus has led to the field getting a bit stuck.

Many scientists have thought that the size of the tiny holes, or nanopores, in the carbon electrodes was the key to improved energy capacity. However, the Cambridge team analysed a series of commercially available nanoporous carbon electrodes and found there was no link between pore size and storage capacity.

Forse and his colleagues took a new approach and used nuclear magnetic resonance (NMR) spectroscopy – a sort of ‘MRI’ for batteries – to study the electrode materials. They found that the messiness of the materials – long thought to be a hindrance – was the key to their success.

“Using NMR spectroscopy, we found that energy storage capacity correlates with how disordered the materials are – the more disordered materials can store more energy,” said first author Xinyu Liu, a PhD candidate co-supervised by Forse and Professor Dame Clare Grey. “Messiness is hard to measure – it’s only possible thanks to new NMR and simulation techniques, which is why messiness is a characteristic that’s been overlooked in this field.”

When analysing the electrode materials with NMR spectroscopy, a spectrum with different peaks and valleys is produced. The position of the peak indicates how ordered or disordered the carbon is. “It wasn’t our plan to look for this, it was a big surprise,” said Forse. “When we plotted the position of the peak against energy capacity, a striking correlation came through – the most disordered materials had a capacity almost double that of the most ordered materials.”

So why is mess good? Forse says that’s the next thing the team is working on. More disordered carbons store ions more efficiently in their nanopores, and the team hope to use these results to design better supercapacitors. The messiness of the materials is determined at the point they are synthesised.

“We want to look at new ways of making these materials, to see how far messiness can take you in terms of improving energy storage,” said Forse. “It could be a turning point for a field that’s been stuck for a little while. Clare and I started working on this topic over a decade ago, and it’s exciting to see a lot of our previous fundamental work now having a clear application.”

The research was supported in part by the Cambridge Trusts, the European Research Council, and UK Research and Innovation (UKRI).

Reference:
Xinyu Liu et al. ‘Structural disorder determines capacitance in nanoporous carbons.’ Science (2024). DOI: 10.1126/science.adn6242

For more information on energy-related research in Cambridge, please visit the Energy IRC, which brings together Cambridge’s research knowledge and expertise, in collaboration with global partners, to create solutions for a sustainable and resilient energy landscape for generations to come. 

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A study has found that the AI model GPT-4 significantly exceeds the ability of non-specialist doctors to assess eye problems and provide advice.

We could realistically deploy AI in triaging patients with eye issues to decide which cases are emergencies.Arun Thirunavukarasu

The clinical knowledge and reasoning skills of GPT-4 are approaching the level of specialist eye doctors, a study led by the University of Cambridge has found.

GPT-4 – a ‘large language model’ – was tested against doctors at different stages in their careers, including unspecialised junior doctors, and trainee and expert eye doctors. Each was presented with a series of 87 patient scenarios involving a specific eye problem, and asked to give a diagnosis or advise on treatment by selecting from four options.

GPT-4 scored significantly better in the test than unspecialised junior doctors, who are comparable to general practitioners in their level of specialist eye knowledge.

GPT-4 gained similar scores to trainee and expert eye doctors – although the top performing doctors scored higher.

The researchers say that large language models aren’t likely to replace healthcare professionals, but have the potential to improve healthcare as part of the clinical workflow.

They say state-of-the-art large language models like GPT-4 could be useful for providing eye-related advice, diagnosis, and management suggestions in well-controlled contexts, like triaging patients, or where access to specialist healthcare professionals is limited.

“We could realistically deploy AI in triaging patients with eye issues to decide which cases are emergencies that need to be seen by a specialist immediately, which can be seen by a GP, and which don’t need treatment,” said Dr Arun Thirunavukarasu, lead author of the study, which he carried out while a student at the University of Cambridge’s School of Clinical Medicine.

He added: “The models could follow clear algorithms already in use, and we’ve found that GPT-4 is as good as expert clinicians at processing eye symptoms and signs to answer more complicated questions.

“With further development, large language models could also advise GPs who are struggling to get prompt advice from eye doctors. People in the UK are waiting longer than ever for eye care.

Large volumes of clinical text are needed to help fine-tune and develop these models, and work is ongoing around the world to facilitate this.

The researchers say that their study is superior to similar, previous studies because they compared the abilities of AI to practicing doctors, rather than to sets of examination results.

“Doctors aren’t revising for exams for their whole career. We wanted to see how AI fared when pitted against to the on-the-spot knowledge and abilities of practicing doctors, to provide a fair comparison,” said Thirunavukarasu, who is now an Academic Foundation Doctor at Oxford University Hospitals NHS Foundation Trust.

He added: “We also need to characterise the capabilities and limitations of commercially available models, as patients may already be using them – rather than the internet – for advice.”

The test included questions about a huge range of eye problems, including extreme light sensitivity, decreased vision, lesions, itchy and painful eyes, taken from a textbook used to test trainee eye doctors. This textbook is not freely available on the internet, making it unlikely that its content was included in GPT-4’s training datasets.

The results are published today in the journal PLOS Digital Health.

“Even taking the future use of AI into account, I think doctors will continue to be in charge of patient care. The most important thing is to empower patients to decide whether they want computer systems to be involved or not. That will be an individual decision for each patient to make,” said Thirunavukarasu.

GPT-4 and GPT-3.5 – or ‘Generative Pre-trained Transformers’ – are trained on datasets containing hundreds of billions of words from articles, books, and other internet sources. These are two examples of large language models; others in wide use include Pathways Language Model 2 (PaLM 2) and Large Language Model Meta AI 2 (LLaMA 2).

The study also tested GPT-3.5, PaLM2, and LLaMA with the same set of questions. GPT-4 gave more accurate responses than all of them.

GPT-4 powers the online chatbot ChatGPT to provide bespoke responses to human queries. In recent months, ChatGPT has attracted significant attention in medicine for attaining passing level performance in medical school examinations, and providing more accurate and empathetic messages than human doctors in response to patient queries.

The field of artificially intelligent large language models is moving very rapidly. Since the study was conducted, more advanced models have been released – which may be even closer to the level of expert eye doctors.

Reference: Thirunavukarasu, A J et al: ‘Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study.’ PLOS Digital Health, April 2024. DOI: 10.1371/journal.pdig.0000341

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An expert on the environmental impacts of aviation, Barrett joins the University of Cambridge from MIT.

It’s a pleasure to welcome Steven back to Cambridge to take up one of the University’s most prestigious rolesVice-Chancellor Professor Deborah Prentice

Professor Steven Barrett has been appointed Regius Professor of Engineering at the University of Cambridge, effective 1 June. He joins the University from the Massachusetts Institute of Technology (MIT), where he is head of the Department of Aeronautics and Astronautics (AeroAstro).

Barrett’s appointment marks his return to Cambridge, where he was an undergraduate at Pembroke College, and received his PhD. He was a Lecturer in the Department of Engineering from 2008 until 2010, when he joined the faculty at MIT.

The Regius Professorships are royal academic titles created by the monarch. The Regius Professorship in Engineering was announced in 2011, in honour of HRH Prince Philip, The Duke of Edinburgh’s 35 years as Chancellor of the University.

“It’s a pleasure to welcome Steven back to Cambridge to take up one of the University’s most prestigious roles,” said Vice-Chancellor Professor Deborah Prentice. “His work on sustainable aviation will build on Cambridge’s existing strengths, and will help us develop the solutions we need to address the threat posed by climate change.”

Barrett’s research focuses on the impact aviation has on the environment. He has developed a number of solutions to mitigate the impact aviation has on air quality, climate, and noise pollution. The overall goal of his research is to help develop technologies that eliminate the environmental impact of aviation. His work on the first-ever plane with no moving propulsion parts was named one of the 10 Breakthroughs of 2018 by Physics World.

“This is an exciting time to work on sustainable aviation, and Cambridge, as well as the UK more generally, is a wonderful platform to advance that,” said Barrett. “Cambridge’s multidisciplinary Department of Engineering, as well as the platform that the Regius Professorship provides, makes this a great opportunity. I’ve learned a lot at MIT, but I’d always hoped to come back to Cambridge at some point.”

Much of Barrett’s research focuses on the elimination of contrails, line-shaped clouds produced by aircraft engine exhaust in cold and humid conditions. Contrails cause half of all aviation-related global warming – more than the entirety of the UK economy. Barrett uses a combination of satellite observation and machine learning techniques to help determine whether avoiding certain regions of airspace could reduce or eliminate contrail formation.

“It will take several years to make this work, but if it does, it could drastically reduce emissions at a very low cost to the consumer,” said Barrett. “We could make the UK the first ‘Blue Skies’ country in the world – the first without any contrails in the sky.”

“Steven’s pioneering work on contrail formation and avoidance is a key element in reducing the environmental impact of aviation, and will strengthen the UK’s position as a world leader in this area,” said Professor Colm Durkan, Head of Cambridge’s Department of Engineering. “Together with Steven’s work on alternative aviation propulsion systems, this will strengthen Cambridge’s vision of helping us all achieve net zero at an accelerated rate.”

In addition to the Professorship in Engineering, there are seven other Regius Professorships at Cambridge: Divinity, Hebrew, Greek, Civil Law and Physic (all founded by Henry VIII in 1540), History (founded by George I in 1724) and Botany (founded in 2009, to mark the University’s 800th anniversary).

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Researchers have used artificial intelligence techniques to massively accelerate the search for Parkinson’s disease treatments.

Machine learning is having a real impact on drug discovery – it’s speeding up the whole process of identifying the most promising candidatesMichele Vendruscolo

The researchers, from the University of Cambridge, designed and used an AI-based strategy to identify compounds that block the clumping, or aggregation, of alpha-synuclein, the protein that characterises Parkinson’s.

The team used machine learning techniques to quickly screen a chemical library containing millions of entries, and identified five highly potent compounds for further investigation.

Parkinson’s affects more than six million people worldwide, with that number projected to triple by 2040. No disease-modifying treatments for the condition are currently available. The process of screening large chemical libraries for drug candidates – which needs to happen well before potential treatments can be tested on patients – is enormously time-consuming and expensive, and often unsuccessful.

Using machine learning, the researchers were able to speed up the initial screening process ten-fold, and reduce the cost by a thousand-fold, which could mean that potential treatments for Parkinson’s reach patients much faster. The results are reported in the journal Nature Chemical Biology.

Parkinson’s is the fastest-growing neurological condition worldwide. In the UK, one in 37 people alive today will be diagnosed with Parkinson’s in their lifetime. In addition to motor symptoms, Parkinson’s can also affect the gastrointestinal system, nervous system, sleeping patterns, mood and cognition, and can contribute to a reduced quality of life and significant disability.

Proteins are responsible for important cell processes, but when people have Parkinson’s, these proteins go rogue and cause the death of nerve cells. When proteins misfold, they can form abnormal clusters called Lewy bodies, which build up within brain cells stopping them from functioning properly.

“One route to search for potential treatments for Parkinson’s requires the identification of small molecules that can inhibit the aggregation of alpha-synuclein, which is a protein closely associated with the disease,” said Professor Michele Vendruscolo from the Yusuf Hamied Department of Chemistry, who led the research. “But this is an extremely time-consuming process – just identifying a lead candidate for further testing can take months or even years.”

While there are currently clinical trials for Parkinson’s currently underway, no disease-modifying drug has been approved, reflecting the inability to directly target the molecular species that cause the disease.

This has been a major obstacle in Parkinson’s research, because of the lack of methods to identify the correct molecular targets and engage with them. This technological gap has severely hampered the development of effective treatments.

The Cambridge team developed a machine learning method in which chemical libraries containing millions of compounds are screened to identify small molecules that bind to the amyloid aggregates and block their proliferation.

A small number of top-ranking compounds were then tested experimentally to select the most potent inhibitors of aggregation. The information gained from these experimental assays was fed back into the machine learning model in an iterative manner, so that after a few iterations, highly potent compounds were identified.

“Instead of screening experimentally, we screen computationally,” said Vendruscolo, who is co-Director of the Centre for Misfolding Diseases. “By using the knowledge we gained from the initial screening with our machine learning model, we were able to train the model to identify the specific regions on these small molecules responsible for binding, then we can re-screen and find more potent molecules.”

Using this method, the Cambridge team developed compounds to target pockets on the surfaces of the aggregates, which are responsible for the exponential proliferation of the aggregates themselves. These compounds are hundreds of times more potent, and far cheaper to develop, than previously reported ones.

“Machine learning is having a real impact on drug discovery – it’s speeding up the whole process of identifying the most promising candidates,” said Vendruscolo. “For us, this means we can start work on multiple drug discovery programmes – instead of just one. So much is possible due to the massive reduction in both time and cost – it’s an exciting time.”

The research was conducted in the Chemistry of Health Laboratory in Cambridge, which was established with the support of the UK Research Partnership Investment Fund (UKRPIF) to promote the translation of academic research into clinical programmes.

Reference:
Robert I Horne et al. ‘Discovery of Potent Inhibitors of α-Synuclein Aggregation Using Structure-Based Iterative Learning.’ Nature Chemical Biology (2024). DOI: 10.1038/s41589-024-01580-x

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Quantum leap

By Sarah Fell

source: www.cam.ac.uk

WHO? Founder and CEO of Cambridge spinout, Nu Quantum, Carmen Palacios-Berraquero, has a PhD in physics from Cambridge and is the recipient of numerous accolades, including the Jocelyn Bell Burnell Medal and Prize for exceptional early-career contributions to physics by a female physicist.

She is also a founding member and Director of UKQuantum, the voice of the UK’s quantum industry and a member of the Technical Advisory Group to UKRI’s National Quantum Computing Centre.

WHAT? Building the quantum networking infrastructure essential to scaling quantum
computers.

WHY? “Quantum computing is going to be the defining technology of this century. It’s a privilege to be in this moment of time, developing this technology which is going to change everything.”

Why did your parents decide to educate you in a British School in Madrid? Both my parents are medical doctors. My dad in particular has always done cancer research but he struggled with having to learn English later on in life. It was always front of mind for him that he wanted his daughters not to have to worry about that.

From a very early age, I knew I wanted to study physics – and to do so abroad. Having had a British education made me think of applying to Imperial for my first degree.

Did you always want to do a PhD? It was pretty clear to me that I would do one. After my degree, I was accepted into two PhD programmes – one here and one in Oxford. I chose Cambridge, joining the Nanotechnology Centre for Doctoral Training (CDT).

That meant doing a master’s before starting the PhD. That first year was great: I had a lot of fun and it gave me a chance to understand how research works, the kinds of things people research and what my options might be.

Even though I was part of the Nanotechnology CDT, quantum physics was always my favourite subject so that’s where I ended up. My supervisor, Professor Mete Atatüre, said: “There’s this new thing – 2D materials and quantum optics – do you want to do it?” It sounded perfect, a new field, ripe for research.

My PhD was very successful. I published two highly cited first author papers and filed a patent.

At this point, did you think you were on a conventional academic career path? By the time I got to Cambridge, I definitely thought I would pursue an academic career, become a professor and all that.

What changed your mind? I became disillusioned with academia. I didn’t really feel like I wanted to carry on and apply for a postdoc position.

For a while, I continued to work on a really challenging experimental project but Cambridge Enterprise (the University’s technology transfer arm) kept asking me what I was planning to do with the patent I had filed during my PhD.

They suggested that I go on the University’s Impulse programme. By the time the programme finished, everything started to snowball.

“I suddenly realised that this is quite fun and I’m quite good at it.”

I began to understand more about the quantum industry. 2018 felt transitional – it was, in fact, when the majority of quantum start-ups were founded: it seemed like the moment when research leaves academia and goes out into the real world.

I was asked to pitch at an event in London. An investor saw me and invited me to join an accelerator programme, even though it was for Series A companies and I didn’t even have a piece of paper with the company name on it.

In September 2018, I incorporated the company just so that I could go on that programme. I started to work with the entrepreneur in residence there, applied for a small grant and was given £20k by Cambridge Enterprise. I suddenly realised that this is quite fun and I’m quite good at it.

It sounds as if you had to be persuaded that founding a company was a good idea? Kind of. I gradually became less sceptical over time. Now, I absolutely love it!

“Quantum computing is going to be the defining technology of this century.”

Can you explain – in simple terms – what Nu Quantum does? We believe quantum computing is going to be transformational, the defining technology of this century, much like classical computers were in the last one.

Instead of the binary logic we are used to in computing – zeros and ones – in quantum, we have qubits (short for quantum bits). These qubits can be entangled together creating multi-qubit superposition states. Essentially, in very simplified terms, this could mean that you are able to explore an exponentially large number of solutions to a problem at the same time.

The problem is that it’s really hard to build these computers. A qubit is embodied in an object such as a single atom: assembling and controlling them is difficult as quantum states are very fragile. Qubits need to be completely isolated from everything and their interactions controlled super-precisely which is why we need advanced infrastructure such as an array of fridges, lasers and ultra-high vacuum systems.

And because qubits are not perfect we need many of them – around a million – to make the kind of calculations we think will be life-changing.

At the moment, we are managing around 100 qubits in one machine. We think we can get to thousands per machine in the next five years. But that’s still orders of magnitude from where we need to be.

So we need to think about a modular approach, with many computers connected together. The analogy is with high-performance compute clusters which are also modular, with many, many computing cores all connected together.

A quantum network extends the entanglement that exists inside each individual quantum computing unit, and creates entanglement so that all the modules can work together to carry out a larger computation.

This is what we are doing, building these quantum computing networks so that we can scale quantum computers. Unsurprisingly, it’s very hard to do.

How do you think quantum computing is going to change our lives? In lots of ways but some of the most exciting applications are likely to be in designing new materials and optimising drugs in ways, and at speeds, which are out of reach today.

What are you most excited about? Everything. We are one of the only quantum networking companies in the world. Without this technology the world won’t be able to build quantum computers. We are designing how to inter-connect quantum computers, what the different parts of a modular architecture are, what they are called and how the protocols work. It’s a privilege to be in this moment in time, developing this technology.

“I’ve learnt that there are constant problems but also constant successes: it’s not like you ever arrive at a steady state.”

How have you found growing the team? It’s been great. We have tripled in size in the last 12 months.

Nine months ago, hiring was the number one risk because we had several new projects and contracts and so we had to grow fast and that’s hard to do but we’ve done it. We’ve hired an amazing team.

Has being in Cambridge helped with that? For sure. Half of our technical team are physics and quantum PhDs and the other half are industry engineers. Some of our scientists come from the University and they are very international. Our engineers, on the other hand, tend to come from other great technology companies around Cambridge.

Cambridge and the UK more widely is an attractive place for people to move to, which really helps.

You clearly love physics and quantum. Are you getting enough of that now that you’re growing so fast? I do a bit of everything. It’s been a long time since I did any deep, detailed implementation of the technology in the lab but I’m involved in all functions of the business at the right level.

My role is understanding where the company needs to go to be successful commercially and ensuring that we are all rowing in the same direction. It’s about understanding both the industry and the technology.

I’m very lucky with my management team. Everyone in my team is an expert in their field. I trust them – and they trust me.

How competitive is the UK’s quantum industry? The UK is one of the top countries in terms of funding, the number of patents, the number of companies and the level of government support. The other big players are the US, China, Canada, and Europe. The US is very strong with big tech companies investing in quantum like Cisco, Google, IBM and Intel but the UK has the opportunity to have some world-leading players and I hope Nu Quantum will be one of them.

Who’s influenced or inspired you? I learn from my management team every day as well as from my investors.

What are you most proud of? The team and the strategy. We didn’t start out on this path – we’ve had a major pivot. We had seen something that no-one else had seen, we moved there early and we are now doing the work of creating this category.

What about setbacks? Pre-pivot it was hard for many reasons, not least during the pandemic when all our labs were closed.

And it continues to be hard. There are always going to be problems.

What have you learnt? So much. It turns out that I’m way more commercially minded than I thought and now what I bring is the commercial strategy and building partnerships.

I’ve also learnt that there are constant problems to solve but also constant successes: it’s not like you ever arrive at a steady state.

What would your colleagues say is your greatest strength? Maybe something to do with drive or energy? Also that I enjoy problem-solving on a massive scale.

What about weaknesses? The other side of the coin is that I can be too driven, which may spill over into impatience.

Do you have a piece of advice for someone who is interested in starting a business? Give it a go!

What do you like doing in your spare time? Dancing and spending time with my friends and family

Quick fire

Optimist or pessimist? Optimist.
People or ideas? It has to be people.
On time or running late? Roughly on time which is maybe five minutes late.
The journey or the destination? The journey.
Team player or lone wolf? Team player.
Novelty or routine? Novelty.
Big picture or fine detail? Big picture.
Do you have to be lucky or make your own luck? Make your own luck.
Work, work, work or work-life balance? Work-life balance. I like to have fun.

Enterprising Minds has been developed with the help of Bruno Cotta, Visiting Fellow & Honorary Ambassador at the Cambridge Judge Business School.

Published 21 March 2024

_{All photography: StillVision}

_{The text in this work is licensed under a Creative Commons Attribution 4.0 International License.}