Webb detects most distant black hole merger to date
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.
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 ÜblerESA/Webb, NASA, CSA, J. Dunlop, H. Übler, R. Maiolino, et. alThe environment of the galaxy system ZS7 from the JWST PRIMER programme as seen by Webb's NIRCam instrument
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Nine Cambridge scientists elected as Fellows of the Royal Society 2024
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:
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.
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.
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 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 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.
Nine 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.
Royal SocietyThe Royal Society in central London
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2023 was the hottest summer in two thousand years
Although 2023 has been reported as the hottest year on record, the instrumental evidence only reaches back as far as 1850 at best, and most records are limited to certain regions.
Now, by using past climate information from annually resolved tree rings over two millennia, scientists from the University of Cambridge and the Johannes Gutenberg University Mainz have shown how exceptional the summer of 2023 was.
Even allowing for natural climate variations over hundreds of years, 2023 was still the hottest summer since the height of the Roman Empire, exceeding the extremes of natural climate variability by half a degree Celsius.
“When you look at the long sweep of history, you can see just how dramatic recent global warming is,” said co-author Professor Ulf Büntgen, from Cambridge’s Department of Geography. “2023 was an exceptionally hot year, and this trend will continue unless we reduce greenhouse gas emissions dramatically.”
The results, reported in the journal Nature, also demonstrate that in the Northern Hemisphere, the 2015 Paris Agreement to limit warming to 1.5C above pre-industrial levels has already been breached.
Early instrumental temperature records, from 1850-1900, are sparse and inconsistent. The researchers compared early instrumental data with a large-scale tree ring dataset and found the 19th century temperature baseline used to contextualise global warming is several tenths of a degree Celsius colder than previously thought. By re-calibrating this baseline, the researchers calculated that summer 2023 conditions in the Northern Hemisphere were 2.07C warmer than mean summer temperatures between 1850 and 1900.
“Many of the conversations we have around global warming are tied to a baseline temperature from the mid-19th century, but why is this the baseline? What is normal, in the context of a constantly-changing climate, when we’ve only got 150 years of meteorological measurements?” said Büntgen. “Only when we look at climate reconstructions can we better account for natural variability and put recent anthropogenic climate change into context.”
Tree rings can provide that context, since they contain annually-resolved and absolutely-dated information about past summer temperatures. Using tree-ring chronologies allows researchers to look much further back in time without the uncertainty associated with some early instrumental measurements.
The available tree-ring data reveals that most of the cooler periods over the past 2000 years, such as the Little Antique Ice Age in the 6th century and the Little Ice Age in the early 19th century, followed large-sulphur-rich volcanic eruptions. These eruptions spew huge amounts of aerosols into the stratosphere, triggering rapid surface cooling. The coldest summer of the past two thousand years, in 536 CE, followed one such eruption, and was 3.93C colder than the summer of 2023.
Most of the warmer periods covered by the tree ring data can be attributed to the El Niño climate pattern, or El Niño-Southern Oscillation (ENSO). El Niño affects weather worldwide due to weakened trade winds in the Pacific Ocean and often results in warmer summers in the Northern Hemisphere. While El Niño events were first noted by fisherman in the 17th century, they can be observed in the tree ring data much further back in time.
However, over the past 60 years, global warming caused by greenhouse gas emissions are causing El Niño events to become stronger, resulting in hotter summers. The current El Niño event is expected to continue into early summer 2024, making it likely that this summer will break temperature records once again.
“It’s true that the climate is always changing, but the warming in 2023, caused by greenhouse gases, is additionally amplified by El Niño conditions, so we end up with longer and more severe heat waves and extended periods of drought,” said Professor Jan Esper, the lead author of the study from the Johannes Gutenberg University Mainz in Germany. “When you look at the big picture, it shows just how urgent it is that we reduce greenhouse gas emissions immediately.”
The researchers note that while their results are robust for the Northern Hemisphere, it is difficult to obtain global averages for the same period since data is sparse for the Southern Hemisphere. The Southern Hemisphere also responds differently to climate change, since it is far more ocean-covered than the Northern Hemisphere.
The research was supported in part by the European Research Council.
Reference:
Jan Esper, Max Torbenson, Ulf Büntgen. ‘2023 summer warmth unparalleled over the past 2,000 years.’ Nature (2024). DOI: 10.1038/s41586-024-07512-y
Researchers have found that 2023 was the hottest summer in the Northern Hemisphere in the past two thousand years, almost four degrees warmer than the coldest summer during the same period.
When you look at the long sweep of history, you can see just how dramatic recent global warming isUlf Büntgentrekandshoot via Getty ImagesMorning sun over Los Angeles
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Over 20,000 people join search for new dementia treatments
Using the resource, scientists have already been able to show for the first time that two important bodily mechanisms – inflammation and metabolism – play a role in the decline in brain function as we age.
By 2050, approximately 139 million people are expected to be living with dementia worldwide. In the UK, in 2022, UK Prime Minister launched the Dame Barbara Windsor Dementia Mission, part of the government’s commitment to double increase research funding for dementia.
Although there has been recent progress developing drugs that slow down progression of the disease, the two leading treatments only have a small effect, and the vast majority of new approaches that work in animal studies fail when it comes to patient clinical trials.
One explanation for these failures is that the drugs are tested in people who already have memory loss – and by this point, it may be too late to stop or reverse the disease. Hence, there is an urgent need to understand what is going on before people develop symptoms at the very early stages of disease, and to test new treatments before people come to their doctor with cognitive problems. This approach requires a large cohort of participants willing to be recalled for clinical and experimental studies of cognitive decline.
Today, writing in the journal Nature Medicine, scientists led by the University of Cambridge in partnership with the Alzheimer’s Society report how they have recruited 21,000 people aged 17-85 to the Genes and Cognition Cohort within the National Institute for Health and Care Research (NIHR) BioResource.
The NIHR BioResource was established in 2007 to recruit volunteers keen to engage in experimental medicine and clinical trials across the whole of medicine. Approximately half of its participants are recruited to disease specific cohorts, but the other half are from the general public, and detailed information about their genetics and their physical makeup has been collected. They have all given their consent to be contacted about future research studies.
For the Genes and Cognition Cohort, researchers used a combination of cognitive tests and genetic data, combined with other health data and demographic information, to enable the first at-scale study of cognitive changes. This will allow the team to recruit participants for studies of cognitive decline and new treatments for this.
For example, a pharmaceutical company with a promising new drug candidate to slow the cognitive decline could recruit people through the BioResource based on their profile and invite them to join in the clinical trial. Having a baseline measurement for their cognitive performance will allow scientists to observe whether the drug slows their expected cognitive decline.
Professor Patrick Chinnery from the Department of Clinical Neurosciences at the University of Cambridge and co-Chair of the NIHR BioResource, who has led the project, said: “We’ve created a resource that is unmatched anywhere else in the world, recruiting people who are not showing any signs of dementia rather than people already having symptoms. It will allow us to match individuals to particular studies and speed up the development of much-needed new drugs to treat dementia.
“We know that over time our cognitive function decreases, so we’ve plotted out the expected trajectory of various different cognitive functions over our volunteers’ life course according to their genetic risk. We’ve also asked the question, ‘What are the genetic mechanisms that predispose you to slow or fast cognitive decline as you age?’.”
Using the research, the team have identified two mechanisms that appear to affect cognition as we age and could serve as potential targets to slow down cognitive decline and thereby delay the onset of dementia. The first of these is inflammation, with immune cells specific to the brain and central nervous system – known as microglia – causing gradual deterioration of the brain and hence its ability to perform key cognitive functions. The second mechanism relates to metabolism – in particular, how carbohydrates are broken down in the brain to release energy.
Professor Chinnery added: “Cognitive decline is a natural process, but when it drops below a particular threshold, that’s when there’s a problem – that is when we would diagnose dementia. Anything that slows that decline will delay when we drop below that threshold. If you could put off the onset of dementia from 65 to 75 or even 85, it would make a huge difference at an individual and at a population level.”
Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said: “This exciting study, funded by Alzheimer’s Society, is an important step in helping us to better understand how the diseases that cause dementia begin, and will aid in the development of new treatments that target the early stages of these diseases.
“The data, from over 20,000 volunteers, helps us to better understand the connection between participants’ genes and cognitive decline and allows for further ground-breaking analysis in future.
“One in three people born in the UK today will go on to develop dementia in their lifetime but research will beat dementia. We need to make it a reality sooner through more funding, partnership working and people taking part in dementia research.”
For further information about how you can join the BioResource and contribute to studies like this one and many others, please visit www.bioresource.nihr.ac.uk.
The research was carried out in collaboration with the Medical Research Council Biostatistics Unit and was supported by the Alzheimer’s Society and the NIHR BioResource. The researchers were also supported by Wellcome and the Medical Research Council.
Reference
Rahman, MS et al. Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition Cohort participants. Nat Med; 14 May 2024; DOI: 10.1038/s41591-024-02960-5
More than 20,000 volunteers have been recruited to a resource aimed at speeding up the development of much-needed dementia drugs. The cohort will enable scientists in universities and industry to involve healthy individuals who may be at increased risk of dementia in clinical trials to test whether new drugs can slow the decline in various brain functions including memory and delay the onset of dementia.
We’ve created a resource that is unmatched anywhere else in the world, recruiting people who are not showing any signs of dementia rather than people already having symptomsPatrick ChinneryHalfpoint Images (Getty Images)Smiling elderly woman speaking to a healthcare worker
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Birth by C-section more than doubles odds of measles vaccine failure
A study by the University of Cambridge, UK, and Fudan University, China, has found that a single dose of the measles jab is up to 2.6 times more likely to be completely ineffective in children born by C-section, compared to those born naturally.
Failure of the vaccine means that the child’s immune system does not produce antibodies to fight against measles infection, so they remain susceptible to the disease.
A second measles jab was found to induce a robust immunity against measles in C-section children.
Measles is a highly infectious disease, and even low vaccine failure rates can significantly increase the risk of an outbreak.
A potential reason for this effect is linked to the development of the infant’s gut microbiome – the vast collection of microbes that naturally live inside the gut. Other studies have shown that vaginal birth transfers a greater variety of microbes from mother to baby, which can boost the immune system.
“We’ve discovered that the way we’re born - either by C-section or natural birth - has long-term consequences on our immunity to diseases as we grow up,” said Professor Henrik Salje in the University of Cambridge’s Department of Genetics, joint senior author of the report.
He added: “We know that a lot of children don't end up having their second measles jab, which is dangerous for them as individuals and for the wider population.
“Infants born by C-section are the ones we really want to be following up to make sure they get their second measles jab, because their first jab is much more likely to fail.”
The results are published today in the journal Nature Microbiology.
At least 95% of the population needs to be fully vaccinated to keep measles under control but the UK is well below this, despite the Measles, Mumps and Rubella (MMR) vaccine being available through the NHS Routine Childhood Immunisation Programme.
An increasing number of women around the world are choosing to give birth by caesarean section: in the UK a third of all births are by C-section, in Brazil and Turkey over half of all children are born this way.
“With a C-section birth, children aren’t exposed to the mother’s microbiome in the same way as with a vaginal birth. We think this means they take longer to catch up in developing their gut microbiome, and with it, the ability of the immune system to be primed by vaccines against diseases including measles,” said Salje.
To get their results, the researchers used data from previous studies of over 1,500 children in Hunan, China, which included blood samples taken every few weeks from birth to the age of 12. This allowed them to see how levels of measles antibodies in the blood change over the first few years of life, including following vaccination.
They found that 12% of children born via caesarean section had no immune response to their first measles vaccination, as compared to 5% of children born by vaginal delivery. This means that many of the children born by C-section did still mount an immune response following their first vaccination.
Two doses of the measles jab are needed for the body to mount a long-lasting immune response and protect against measles. According to the World Health Organisation, in 2022 only 83% of the world's children had received one dose of measles vaccine by their first birthday – the lowest since 2008.
Salje said: “Vaccine hesitancy is really problematic, and measles is top of the list of diseases we’re worried about because it’s so infectious.”
Measles is one of the world’s most contagious diseases, spread by coughs and sneezes. It starts with cold-like symptoms and a rash, and can lead to serious complications including blindness, seizures, and death.
Before the measles vaccine was introduced in 1963, there were major measles epidemics every few years causing an estimated 2.6 million deaths each year.
The research was funded by the National Natural Science Foundation of China.
Reference
Wang, W. et al: ‘Dynamics of measles immunity from birth and following vaccination.’ Nature Microbiology, 13 May 2024. DOI: 10.1038/s41564-024-01694-x
Researchers say it is vital that children born by caesarean section receive two doses of the measles vaccine for robust protection against the disease.
CHBD / E+ / Getty Images Very sick 5 year old little boy fighting measles infection, boy is laying in bed under the blanket with a agonizing expression, boy is covered with rash caused by virus.
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Baby born deaf can hear after breakthrough gene therapy
Opal Sandy from Oxfordshire is the first patient treated in a global gene therapy trial, which shows “mind-blowing” results. She is the first British patient in the world and the youngest child to receive this type of treatment.
Opal was born completely deaf because of a rare genetic condition, auditory neuropathy, caused by the disruption of nerve impulses travelling from the inner ear to the brain.
Within four weeks of having the gene therapy infusion to her right ear, Opal responded to sound, even with the cochlear implant in her left ear switched off.
Clinicians noticed continuous improvement in Opal’s hearing in the weeks afterwards. At 24 weeks, they confirmed Opal had close to normal hearing levels for soft sounds, such as whispering, in her treated ear.
Now 18 months old, Opal can respond to her parents’ voices and can communicate words such as “Dada” and “bye-bye.”
Opal’s mother, Jo Sandy, said: “When Opal could first hear us clapping unaided it was mind-blowing - we were so happy when the clinical team confirmed at 24 weeks that her hearing was also picking up softer sounds and speech. The phrase ‘near normal’ hearing was used and everyone was so excited such amazing results had been achieved.”
Auditory neuropathy can be due to a variation in a single gene, known as the OTOF gene. The gene produces a protein called otoferlin, needed to allow the inner hair cells in the ear to communicate with the hearing nerve. Approximately 20,000 people across the UK, Germany, France, Spain, Italy and UK and are deaf due to a mutation in the OTOF gene.
The CHORD trial, which started in May 2023, aims to show whether gene therapy can provide hearing for children born with auditory neuropathy.
Professor Manohar Bance from the Department of Clinical Neurosciences at the University of Cambridge and an ear surgeon at Cambridge University Hospitals NHS Foundation Trust is chief investigator of the trial. He said:
“These results are spectacular and better than I expected. Gene therapy has been the future of otology and audiology for many years and I’m so excited that it is now finally here. This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss.”
Children with a variation in the OTOF gene often pass the newborn screening, as the hair cells are working, but they are not talking to the nerve. It means this hearing loss is not commonly detected until children are 2 or 3 years of age – when a delay in speech is likely to be noticed.
Professor Bance added: “We have a short time frame to intervene because of the rapid pace of brain development at this age. Delays in the diagnosis can also cause confusion for families as the many reasons for delayed speech and late intervention can impact a children’s development.”
“More than sixty years after the cochlear implant was first invented – the standard of care treatment for patients with OTOF related hearing loss – this trial shows gene therapy could provide a future alternative. It marks a new era in the treatment for deafness. It also supports the development of other gene therapies that may prove to make a difference in other genetic related hearing conditions, many of which are more common than auditory neuropathy.”
Mutations in the OTOF gene can be identified by standard NHS genetic testing. Opal was identified as being at risk as her older sister has the condition; this was confirmed by genetic test result when she was 3 weeks old.
Opal was given an infusion containing a harmless virus (AAV1). It delivers a working copy of the OTOF gene and is delivered via an injection in the cochlea during surgery under general anaesthesia. During surgery, while Opal was given the gene therapy in right ear, a cochlear implant was fitted in her left ear.
James Sandy, Opal’s father said: “It was our ultimate goal for Opal to hear all the speech sounds. It’s already making a difference to our day-to-day lives, like at bath-time or swimming, when Opal can’t wear her cochlear implant. We feel so proud to have contributed to such pivotal findings, which will hopefully help other children like Opal and their families in the future.”
Opal’s 24-week results, alongside other scientific data from the CHORD trial are being presented at the American Society of Gene and Cell Therapy (ASGC) in Baltimore, USA this week.
Dr Richard Brown, Consultant Paediatrician at CUH, who is an Investigator on the CHORD trial, said: “The development of genomic medicine and alternative treatments is vital for patients worldwide, and increasingly offers hope to children with previously incurable disorders. It is likely that in the long run such treatments require less follow up so may prove to be an attractive option, including within the developing world. Follow up appointments have shown effective results so far with no adverse reactions and it is exciting to see the results to date.
“Within the new planned Cambridge Children’s Hospital, we look forward to having a genomic centre of excellence which will support patients from across the region to access the testing they need, and the best treatment, at the right time.”
The CHORD trial has been funded by Regeneron. Patients are being enrolled in the study in the US, UK and Spain.
Patients in the first phase of the study receive a low dose to one ear. The second phase are expected to use a higher dose of gene therapy in one ear only, following proven safety of the starting dose. The third phase will look at gene therapy in both ears with the dose selected after ensuring the safety and effectiveness in parts 1 and 2. Follow up appointments will continue for five years for enrolled patients, which will show how patients adapt to understand speech in the longer term.
In Cambridge, the trial is supported by NIHR Cambridge Clinical Research Facility and NIHR Cambridge Biomedical Research Centre.
Adapted from a press release from CUH
A baby girl born deaf can hear unaided for the first time, after receiving gene therapy when she was eleven months old at Addenbrooke’s Hospital in Cambridge.
Gene therapy has been the future of otology and audiology for many years and I’m so excited that it is now finally hereManohar BanceCambridge University Hospitals NHS Foundation TrustBaby Opal and mother Jo
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Call for safeguards to prevent unwanted ‘hauntings’ by AI chatbots of dead loved ones
Artificial intelligence that allows users to hold text and voice conversations with lost loved ones runs the risk of causing psychological harm and even digitally “haunting” those left behind without design safety standards, according to University of Cambridge researchers.
‘Deadbots’ or ‘Griefbots’ are AI chatbots that simulate the language patterns and personality traits of the dead using the digital footprints they leave behind. Some companies are already offering these services, providing an entirely new type of “postmortem presence”.
AI ethicists from Cambridge’s Leverhulme Centre for the Future of Intelligence outline three design scenarios for platforms that could emerge as part of the developing “digital afterlife industry”, to show the potential consequences of careless design in an area of AI they describe as “high risk”.
The research, published in the journal Philosophy and Technology, highlights the potential for companies to use deadbots to surreptitiously advertise products to users in the manner of a departed loved one, or distress children by insisting a dead parent is still “with you”.
When the living sign up to be virtually re-created after they die, resulting chatbots could be used by companies to spam surviving family and friends with unsolicited notifications, reminders and updates about the services they provide – akin to being digitally “stalked by the dead”.
Even those who take initial comfort from a ‘deadbot’ may get drained by daily interactions that become an “overwhelming emotional weight”, argue researchers, yet may also be powerless to have an AI simulation suspended if their now-deceased loved one signed a lengthy contract with a digital afterlife service.
“Rapid advancements in generative AI mean that nearly anyone with Internet access and some basic know-how can revive a deceased loved one,” said Dr Katarzyna Nowaczyk-Basińska, study co-author and researcher at Cambridge’s Leverhulme Centre for the Future of Intelligence (LCFI).
“This area of AI is an ethical minefield. It’s important to prioritise the dignity of the deceased, and ensure that this isn’t encroached on by financial motives of digital afterlife services, for example.
“At the same time, a person may leave an AI simulation as a farewell gift for loved ones who are not prepared to process their grief in this manner. The rights of both data donors and those who interact with AI afterlife services should be equally safeguarded.”
Platforms offering to recreate the dead with AI for a small fee already exist, such as ‘Project December’, which started out harnessing GPT models before developing its own systems, and apps including ‘HereAfter’. Similar services have also begun to emerge in China.
One of the potential scenarios in the new paper is “MaNana”: a conversational AI service allowing people to create a deadbot simulating their deceased grandmother without consent of the “data donor” (the dead grandparent).
The hypothetical scenario sees an adult grandchild who is initially impressed and comforted by the technology start to receive advertisements once a “premium trial” finishes. For example, the chatbot suggesting ordering from food delivery services in the voice and style of the deceased.
The relative feels they have disrespected the memory of their grandmother, and wishes to have the deadbot turned off, but in a meaningful way – something the service providers haven’t considered.
“People might develop strong emotional bonds with such simulations, which will make them particularly vulnerable to manipulation,” said co-author Dr Tomasz Hollanek, also from Cambridge’s LCFI.
“Methods and even rituals for retiring deadbots in a dignified way should be considered. This may mean a form of digital funeral, for example, or other types of ceremony depending on the social context.”
“We recommend design protocols that prevent deadbots being utilised in disrespectful ways, such as for advertising or having an active presence on social media.”
While Hollanek and Nowaczyk-Basińska say that designers of re-creation services should actively seek consent from data donors before they pass, they argue that a ban on deadbots based on non-consenting donors would be unfeasible.
They suggest that design processes should involve a series of prompts for those looking to “resurrect” their loved ones, such as ‘have you ever spoken with X about how they would like to be remembered?’, so the dignity of the departed is foregrounded in deadbot development.
Another scenario featured in the paper, an imagined company called “Paren’t”, highlights the example of a terminally ill woman leaving a deadbot to assist her eight-year-old son with the grieving process.
While the deadbot initially helps as a therapeutic aid, the AI starts to generate confusing responses as it adapts to the needs of the child, such as depicting an impending in-person encounter.
The researchers recommend age restrictions for deadbots, and also call for “meaningful transparency” to ensure users are consistently aware that they are interacting with an AI. These could be similar to current warnings on content that may cause seizures, for example.
The final scenario explored by the study – a fictional company called “Stay” – shows an older person secretly committing to a deadbot of themselves and paying for a twenty-year subscription, in the hopes it will comfort their adult children and allow their grandchildren to know them.
After death, the service kicks in. One adult child does not engage, and receives a barrage of emails in the voice of their dead parent. Another does, but ends up emotionally exhausted and wracked with guilt over the fate of the deadbot. Yet suspending the deadbot would violate the terms of the contract their parent signed with the service company.
“It is vital that digital afterlife services consider the rights and consent not just of those they recreate, but those who will have to interact with the simulations,” said Hollanek.
“These services run the risk of causing huge distress to people if they are subjected to unwanted digital hauntings from alarmingly accurate AI recreations of those they have lost. The potential psychological effect, particularly at an already difficult time, could be devastating.”
The researchers call for design teams to prioritise opt-out protocols that allow potential users terminate their relationships with deadbots in ways that provide emotional closure.
Added Nowaczyk-Basińska: “We need to start thinking now about how we mitigate the social and psychological risks of digital immortality, because the technology is already here.”
Cambridge researchers lay out the need for design safety protocols that prevent the emerging “digital afterlife industry” causing social and psychological harm.
Tomasz HollanekA visualisation of one of the design scenarios highlighted in the latest paper
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‘Wraparound’ implants represent new approach to treating spinal cord injuries
A team of engineers, neuroscientists and surgeons from the University of Cambridge developed the devices and used them to record the nerve signals going back and forth between the brain and the spinal cord. Unlike current approaches, the Cambridge devices can record 360-degree information, giving a complete picture of spinal cord activity.
Tests in live animal and human cadaver models showed the devices could also stimulate limb movement and bypass complete spinal cord injuries where communication between the brain and spinal cord had been completely interrupted.
Most current approaches to treating spinal injuries involve both piercing the spinal cord with electrodes and placing implants in the brain, which are both high-risk surgeries. The Cambridge-developed devices could lead to treatments for spinal injuries without the need for brain surgery, which would be far safer for patients.
While such treatments are still at least several years away, the researchers say the devices could be useful in the near-term for monitoring spinal cord activity during surgery. Better understanding of the spinal cord, which is difficult to study, could lead to improved treatments for a range of conditions, including chronic pain, inflammation and hypertension. The results are reported in the journal Science Advances.
“The spinal cord is like a highway, carrying information in the form of nerve impulses to and from the brain,” said Professor George Malliaras from the Department of Engineering, who co-led the research. “Damage to the spinal cord causes that traffic to be interrupted, resulting in profound disability, including irreversible loss of sensory and motor functions.”
The ability to monitor signals going to and from the spinal cord could dramatically aid in the development of treatments for spinal injuries, and could also be useful in the nearer term for better monitoring of the spinal cord during surgery.
“Most technologies for monitoring or stimulating the spinal cord only interact with motor neurons along the back, or dorsal, part of the spinal cord,” said Dr Damiano Barone from the Department of Clinical Neurosciences, who co-led the research. “These approaches can only reach between 20 and 30 percent of the spine, so you’re getting an incomplete picture.”
By taking their inspiration from microelectronics, the researchers developed a way to gain information from the whole spine, by wrapping very thin, high-resolution implants around the spinal cord’s circumference. This is the first time that safe 360-degree recording of the spinal cord has been possible – earlier approaches for 360-degree monitoring use electrodes that pierce the spine, which can cause spinal injury.
The Cambridge-developed biocompatible devices – just a few millionths of a metre thick – are made using advanced photolithography and thin film deposition techniques, and require minimal power to function.
The devices intercept the signals travelling on the axons, or nerve fibres, of the spinal cord, allowing the signals to be recorded. The thinness of the devices means they can record the signals without causing any damage to the nerves, since they do not penetrate the spinal cord itself.
“It was a difficult process, because we haven’t made spinal implants in this way before, and it wasn’t clear that we could safely and successfully place them around the spine,” said Malliaras. “But because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important area.”
The devices were implanted using an adaptation to routine surgical procedure so they could be slid under the spinal cord without damaging it. In tests using rat models, the researchers successfully used the devices to stimulate limb movement. The devices showed very low latency – that is, their reaction time was close to human reflexive movement. Further tests in human cadaver models showed that the devices can be successfully placed in humans.
The researchers say their approach could change how spinal injuries are treated in future. Current attempts to treat spinal injuries involve both brain and spinal implants, but the Cambridge researchers say the brain implants may not be necessary.
“If someone has a spinal injury, their brain is fine, but it’s the connection that’s been interrupted,” said Barone. “As a surgeon, you want to go where the problem is, so adding brain surgery on top of spinal surgery just increases the risk to the patient. We can collect all the information we need from the spinal cord in a far less invasive way, so this would be a much safer approach for treating spinal injuries.”
While a treatment for spinal injuries is still years away, in the nearer term, the devices could be useful for researchers and surgeons to learn more about this vital, but understudied, part of human anatomy in a non-invasive way. The Cambridge researchers are currently planning to use the devices to monitor nerve activity in the spinal cord during surgery.
“It’s been almost impossible to study the whole of the spinal cord directly in a human, because it’s so delicate and complex,” said Barone. “Monitoring during surgery will help us to understand the spinal cord better without damaging it, which in turn will help us develop better therapies for conditions like chronic pain, hypertension or inflammation. This approach shows enormous potential for helping patients.”
The research was supported in part by the Royal College of Surgeons, the Academy of Medical Sciences, Health Education England, the National Institute for Health Research, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).
Reference:
Ben J Woodington, Jiang Lei et al. ‘Flexible Circumferential Bioelectronics to Enable 360-degree Recording and Stimulation of the Spinal Cord.’ Science Advances (2024). DOI: 10.1126/sciadv.adl1230
A tiny, flexible electronic device that wraps around the spinal cord could represent a new approach to the treatment of spinal injuries, which can cause profound disability and paralysis.
Because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important areaGeorge MalliarasSEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARYIllustration of spinal cord
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New vaccine effective against coronaviruses that haven’t even emerged yet
This is a new approach to vaccine development called ‘proactive vaccinology’, where scientists build a vaccine before the disease-causing pathogen even emerges.
The new vaccine works by training the body’s immune system to recognise specific regions of eight different coronaviruses, including SARS-CoV-1, SARS-CoV-2, and several that are currently circulating in bats and have potential to jump to humans and cause a pandemic.
Key to its effectiveness is that the specific virus regions the vaccine targets also appear in many related coronaviruses. By training the immune system to attack these regions, it gives protection against other coronaviruses not represented in the vaccine – including ones that haven’t even been identified yet.
For example, the new vaccine does not include the SARS-CoV-1 coronavirus, which caused the 2003 SARS outbreak, yet it still induces an immune response to that virus.
“Our focus is to create a vaccine that will protect us against the next coronavirus pandemic, and have it ready before the pandemic has even started,” said Rory Hills, a graduate researcher in the University of Cambridge’s Department of Pharmacology and first author of the report.
He added: “We’ve created a vaccine that provides protection against a broad range of different coronaviruses – including ones we don’t even know about yet.”
The results are published today in the journal Nature Nanotechnology.
“We don’t have to wait for new coronaviruses to emerge. We know enough about coronaviruses, and different immune responses to them, that we can get going with building protective vaccines against unknown coronaviruses now,” said Professor Mark Howarth in the University of Cambridge’s Department of Pharmacology, senior author of the report.
He added: “Scientists did a great job in quickly producing an extremely effective COVID vaccine during the last pandemic, but the world still had a massive crisis with a huge number of deaths. We need to work out how we can do even better than that in the future, and a powerful component of that is starting to build the vaccines in advance.”
The new ‘Quartet Nanocage’ vaccine is based on a structure called a nanoparticle – a ball of proteins held together by incredibly strong interactions. Chains of different viral antigens are attached to this nanoparticle using a novel ‘protein superglue’. Multiple antigens are included in these chains, which trains the immune system to target specific regions shared across a broad range of coronaviruses.
This study demonstrated that the new vaccine raises a broad immune response, even in mice that were pre-immunised with SARS-CoV-2.
The new vaccine is much simpler in design than other broadly protective vaccines currently in development, which the researchers say should accelerate its route into clinical trials.
The underlying technology they have developed also has potential for use in vaccine development to protect against many other health challenges.
The work involved a collaboration between scientists at the University of Cambridge, the University of Oxford, and Caltech. It improves on previous work, by the Oxford and Caltech groups, to develop a novel all-in-one vaccine against coronavirus threats. The vaccine developed by Oxford and Caltech should enter Phase 1 clinical trials in early 2025, but its complex nature makes it challenging to manufacture which could limit large-scale production.
Conventional vaccines include a single antigen to train the immune system to target a single specific virus. This may not protect against a diverse range of existing coronaviruses, or against pathogens that are newly emerging.
The research was funded by the Biotechnology and Biological Sciences Research Council.
Reference: Hills, R.A. et al: ‘Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.’ Nature Nanotechnology, May 2024. DOI: 10.1038/s41565-024-01655-9
Researchers have developed a new vaccine technology that has been shown in mice to provide protection against a broad range of coronaviruses with potential for future disease outbreaks - including ones we don’t even know about
Our focus is to create a vaccine that will protect us against the next coronavirus pandemic, and have it ready before the pandemic has even started.Rory HillsStefan Cristian Cioata on GettySyringe and vaccine bottle
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Ice shelves fracture under weight of meltwater lakes
When air temperatures in Antarctica rise and glacier ice melts, water can pool on the surface of floating ice shelves, weighing them down and causing the ice to bend. Now, for the first time in the field, researchers have shown that ice shelves don’t just buckle under the weight of meltwater lakes — they fracture.
As the climate warms and melt rates in Antarctica increase, this fracturing could cause vulnerable ice shelves to collapse, allowing inland glacier ice to spill into the ocean and contribute to sea level rise.
Ice shelves are important for the Antarctic Ice Sheet’s overall health as they act to buttress or hold back the glacier ice on land. Scientists have predicted and modelled that surface meltwater loading could cause ice shelves to fracture, but no one had observed the process in the field, until now.
The new study, published in the Journal of Glaciology, may help explain how the Larsen B Ice Shelf abruptly collapsed in 2002. In the months before its catastrophic breakup, thousands of meltwater lakes littered the ice shelf’s surface, which then drained over just a few weeks.
To investigate the impacts of surface meltwater on ice shelf stability, a research team led by the University of Colorado Boulder, and including researchers from the University of Cambridge, travelled to the George VI Ice Shelf on the Antarctic Peninsula in November 2019.
First, the team identified a depression or ‘doline’ in the ice surface that had formed by a previous lake drainage event where they thought meltwater was likely to pool again on the ice. Then, they ventured out on snowmobiles, pulling all their science equipment and safety gear behind on sleds.
Around the doline, the team installed high-precision GPS stations to measure small changes in elevation at the ice’s surface, water-pressure sensors to measure lake depth, and a timelapse camera system to capture images of the ice surface and meltwater lakes every 30 minutes.
In 2020, the COVID-19 pandemic brought their fieldwork to a screeching halt. When the team finally made it back to their field site in November 2021, only two GPS sensors and one timelapse camera remained; two other GPS and all water pressure sensors had been flooded and buried in solid ice. Fortunately, the surviving instruments captured the vertical and horizontal movement of the ice’s surface and images of the meltwater lake that formed and drained during the record-high 2019/2020 melt season.
GPS data indicated that the ice in the centre of the lake basin flexed downward about a foot in response to the increased weight from meltwater. That finding builds upon previous work that produced the first direct field measurements of ice shelf buckling caused by meltwater ponding and drainage.
The team also found that the horizontal distance between the edge and centre of the meltwater lake basin increased by over a foot. This was most likely due to the formation and/or widening of circular fractures around the meltwater lake, which the timelapse imagery captured. Their results provide the first field-based evidence of ice shelf fracturing in response to a surface meltwater lake weighing down the ice.
“This is an exciting discovery,” said lead author Alison Banwell, from the Cooperative Institute for Research in Environmental Sciences (CIRES) at the University of Colorado Boulder. “We believe these types of circular fractures were key in the chain reaction style lake drainage process that helped to break up the Larsen B Ice Shelf.”
“While these measurements were made over a small area, they demonstrate that bending and breaking of floating ice due to surface water may be more widespread than previously thought,” said co-author Dr Rebecca Dell from Cambridge’s Scott Polar Research Institute. “As melting increases in response to predicted warming, ice shelves may become more prone to break up and collapse than they are currently.”
“This has implications for sea level as the buttressing of inland ice is reduced or removed, allowing the glaciers and ice streams to flow more rapidly into the ocean,” said co-author Professor Ian Willis, also from SPRI.
The work supports modelling results that show the immense weight of thousands of meltwater lakes and subsequent draining caused the Larsen B Ice Shelf to bend and break, contributing to its collapse.
“These observations are important because they can be used to improve models to better predict which Antarctic ice shelves are more vulnerable and most susceptible to collapse in the future,” Banwell said.
The research was funded by the U.S. National Science Foundation (NSF) and the Natural Environment Research Council (NERC), part of UK Research and Innovation (UKRI). The team also included researchers from the University of Oxford and the University of Chicago. Rebecca Dell is a Fellow of Trinity Hall, Cambridge.
Reference:
Alison F Banwell et al. ‘Observed meltwater-induced flexure and fracture at a doline on George VI Ice Shelf, Antarctica.’ Journal of Glaciology (2024). DOI: 10.1017/jog.2024.31
Adapted from a CIRES press release.
Heavy pooling meltwater can fracture ice, potentially leading to ice shelf collapse
Ian WillisAli Banwell and Laura Stevens installing the time-lapse camera used in this study on the George VI Ice Shelf in Antarctica.
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Robotic nerve ‘cuffs’ could help treat a range of neurological conditions
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
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 MalliarasXH4D via iStock / Getty Images PlusIllustration of the human nervous system
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Study highlights increased risk of second cancers among breast cancer survivors
For the first time, the research has shown that this risk is higher in people living in areas of greater socioeconomic deprivation.
Breast cancer is the most commonly diagnosed cancer in the UK. Around 56,000 people in the UK are diagnosed each year, the vast majority (over 99%) of whom are women. Improvements in earlier diagnosis and in treatments mean that five year survival rates have been increasing over time, reaching 87% by 2017 in England.
People who survive breast cancer are at risk of second primary cancer, but until now the exact risk has been unclear. Previously published research suggested that women and men who survive breast cancer are at a 24% and 27% greater risk of a non-breast second primary cancer than the wider population respectively. There have been also suggestions that second primary cancer risks differ by the age at breast cancer diagnosis.
To provide more accurate estimates, a team led by researchers at the University of Cambridge analysed data from over 580,000 female and over 3,500 male breast cancer survivors diagnosed between 1995 and 2019 using the National Cancer Registration Dataset. The results of their analysis are published today in Lancet Regional Health – Europe.
First author Isaac Allen from the Department of Public Health and Primary Care at the University of Cambridge said: “It’s important for us to understand to what extent having one type of cancer puts you at risk of a second cancer at a different site. The female and male breast cancer survivors whose data we studied were at increased risk of a number of second cancers. Knowing this can help inform conversations with their care teams to look out for signs of potential new cancers.”
The researchers found significantly increased risks of cancer in the contralateral (that is, unaffected) breast and for endometrium and prostate cancer in females and males, respectively. Females who survived breast cancer were at double the risk of contralateral breast cancer compared to the general population and at 87% greater risk of endometrial cancer, 58% greater risk of myeloid leukaemia and 25% greater risk of ovarian cancer.
Age of diagnosis was important, too – females diagnosed with breast cancer under the age of 50 were 86% more likely to develop a second primary cancer compared to the general population of the same age, whereas women diagnosed after age 50 were at a 17% increased risk. One potential explanation is that a larger number of younger breast cancer survivors may have inherited genetic alterations that increase risk for multiple cancers. For example, women with inherited changes to the BRCA1 and BRCA2 genes are at increased risk of contralateral breast cancer, ovarian and pancreatic cancer.
Females from the most socioeconomically deprived backgrounds were at 35% greater risk of a second primary cancer compared to females from the least deprived backgrounds. These differences were primarily driven by non-breast cancer risks, particularly for lung, kidney, head and neck, bladder, oesophageal and stomach cancers. This may be because smoking, obesity, and alcohol consumption – established risk factors for these cancers – are more common among more deprived groups.
Allen, a PhD student at Clare Hall, added: “This is further evidence of the health inequalities that people from more deprived backgrounds experience. We need to fully understand why they are at greater risk of second cancers so that we can intervene and reduce this risk.”
Male breast cancer survivors were 55 times more likely than the general male population to develop contralateral breast cancer – though the researchers stress that an individual’s risk was still very low. For example, for every 100 men diagnosed with breast cancer at age 50 or over, about three developed contralateral breast cancer during a 25 year period. Male breast cancer survivors were also 58% more likely than the general male population to develop prostate cancer.
Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge, the study’s senior author, said: “This is the largest study to date to look at the risk in breast cancer survivors of developing a second cancer. We were able to carry this out and calculate more accurate estimates because of the outstanding data sets available to researchers through the NHS.”
The research was funded by Cancer Research UK with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.
Cancer Research UK’s senior cancer intelligence manager, Katrina Brown, said: “This study shows us that the risk of second primary cancers is higher in people who have had breast cancer, and this can differ depending on someone’s socioeconomic background. But more research is needed to understand what is driving this difference and how to tackle these health inequalities.”
People who are concerned about their cancer risk should contact their GP for advice. If you or someone close to you have been affected by cancer and you’ve got questions, you can call Cancer Research UK nurses on freephone 0808 800 4040, Monday to Friday.
Reference
Allen, I, et al. Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study. Lancet Regional Health – Europe; 24 April 2024: DOI: 10.1016/j.lanepe.2024.100903
Survivors of breast cancer are at significantly higher risk of developing second cancers, including endometrial and ovarian cancer for women and prostate cancer for men, according to new research studying data from almost 600,000 patients in England.
It’s important for us to understand to what extent having one type of cancer puts you at risk of a second cancer at a different site. Knowing this can help inform conversations with their care teams to look out for signs of potential new cancersIsaac AllenNational Cancer InstituteDoctor standing near woman patient doing breast cancer
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A simple ‘twist’ improves the engine of clean fuel generation
The researchers, led by the University of Cambridge, are developing low-cost light-harvesting semiconductors that power devices for converting water into clean hydrogen fuel, using just the power of the sun. These semiconducting materials, known as copper oxides, are cheap, abundant and non-toxic, but their performance does not come close to silicon, which dominates the semiconductor market.
However, the researchers found that by growing the copper oxide crystals in a specific orientation so that electric charges move through the crystals at a diagonal, the charges move much faster and further, greatly improving performance. Tests of a copper oxide light harvester, or photocathode, based on this fabrication technique showed a 70% improvement over existing state-of-the-art oxide photocathodes, while also showing greatly improved stability.
The researchers say their results, reported in the journal Nature, show how low-cost materials could be fine-tuned to power the transition away from fossil fuels and toward clean, sustainable fuels that can be stored and used with existing energy infrastructure.
Copper (I) oxide, or cuprous oxide, has been touted as a cheap potential replacement for silicon for years, since it is reasonably effective at capturing sunlight and converting it into electric charge. However, much of that charge tends to get lost, limiting the material’s performance.
“Like other oxide semiconductors, cuprous oxide has its intrinsic challenges,” said co-first author Dr Linfeng Pan from Cambridge’s Department of Chemical Engineering and Biotechnology. “One of those challenges is the mismatch between how deep light is absorbed and how far the charges travel within the material, so most of the oxide below the top layer of material is essentially dead space.”
“For most solar cell materials, it’s defects on the surface of the material that cause a reduction in performance, but with these oxide materials, it’s the other way round: the surface is largely fine, but something about the bulk leads to losses,” said Professor Sam Stranks, who led the research. “This means the way the crystals are grown is vital to their performance.”
To develop cuprous oxides to the point where they can be a credible contender to established photovoltaic materials, they need to be optimised so they can efficiently generate and move electric charges – made of an electron and a positively-charged electron ‘hole’ – when sunlight hits them.
One potential optimisation approach is single-crystal thin films – very thin slices of material with a highly-ordered crystal structure, which are often used in electronics. However, making these films is normally a complex and time-consuming process.
Using thin film deposition techniques, the researchers were able to grow high-quality cuprous oxide films at ambient pressure and room temperature. By precisely controlling growth and flow rates in the chamber, they were able to ‘shift’ the crystals into a particular orientation. Then, using high temporal resolution spectroscopic techniques, they were able to observe how the orientation of the crystals affected how efficiently electric charges moved through the material.
“These crystals are basically cubes, and we found that when the electrons move through the cube at a body diagonal, rather than along the face or edge of the cube, they move an order of magnitude further,” said Pan. “The further the electrons move, the better the performance.”
“Something about that diagonal direction in these materials is magic,” said Stranks. “We need to carry out further work to fully understand why and optimise it further, but it has so far resulted in a huge jump in performance.” Tests of a cuprous oxide photocathode made using this technique showed an increase in performance of more than 70% over existing state-of-the-art electrodeposited oxide photocathodes.
“In addition to the improved performance, we found that the orientation makes the films much more stable, but factors beyond the bulk properties may be at play,” said Pan.
The researchers say that much more research and development is still needed, but this and related families of materials could have a vital role in the energy transition.
“There’s still a long way to go, but we’re on an exciting trajectory,” said Stranks. “There’s a lot of interesting science to come from these materials, and it’s interesting for me to connect the physics of these materials with their growth, how they form, and ultimately how they perform.”
The research was a collaboration with École Polytechnique Fédérale de Lausanne, Nankai University and Uppsala University. The research was supported in part by the European Research Council, the Swiss National Science Foundation, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI). Sam Stranks is Professor of Optoelectronics in the Department of Chemical Engineering and Biotechnology, and a Fellow of Clare College, Cambridge.
Reference:
Linfeng Pan, Linjie Dai et al. ‘High carrier mobility along the [111] orientation in Cu2O photoelectrodes.’ Nature (2024). DOI: 10.1038/s41586-024-07273-8
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.
Researchers have found a way to super-charge the ‘engine’ of sustainable fuel generation – by giving the materials a little twist.
orange via Getty ImagesAbstract orange swirls
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Rare disease research at Cambridge receives major boost with launch of two new centres
The virtual centres, supported by the charity LifeArc, will focus on areas where there are significant unmet needs. They will tackle barriers that ordinarily prevent new tests and treatments reaching patients with rare diseases and speed up the delivery of rare disease treatment trials.
The centres will bring together leading scientists and rare disease clinical specialists from across the UK for the first time, encouraging new collaborations across different research disciplines and providing improved access to facilities and training.
LifeArc Centre for Rare Mitochondrial DiseasesProfessor Patrick Chinnery will lead the LifeArc Centre for Rare Mitochondrial Diseases, a national partnership with the Lily Foundation and Muscular Dystrophy UK, together with key partners at UCL, Newcastle University and three other centres (Oxford, Birmingham and Manchester).
Mitochondrial diseases are genetic disorders affecting 1 in 5,000 people. They often cause progressive damage to the brain, eyes, muscles, heart and liver, leading to severe disability and a shorter life. There is currently have no cure for most conditions, however, new opportunities to treat mitochondrial diseases have been identified in the last five years, meaning that it’s a critical time for research development. The £7.5M centre will establish a national platform that will connect patient groups, knowledge and infrastructure in order to accelerate new treatments getting to clinical trial.
Professor Chinnery said: “The new LifeArc centre unites scientific and clinical strengths from across the UK. For the first time we will form a single team, focussed on developing new treatments for mitochondrial diseases which currently have no cure.”
Adam Harraway has Mitochondrial Disease and says he lives in constant fear of what might go wrong next with his condition. “With rare diseases such as these, it can feel like the questions always outweigh the answers. The news of this investment from LifeArc fills me with hope for the future. To know that there are so many wonderful people and organisations working towards treatments and cures makes me feel seen and heard. It gives a voice to people who often have to suffer in silence, and I'm excited to see how this project can help Mito patients in the future."
LifeArc Centre for Rare Respiratory DiseasesProfessor Stefan Marciniak will co-lead the LifeArc Centre for Rare Respiratory Diseases, a UK wide collaborative centre co-created in partnership with patients and charities. This Centre is a partnership between Universities and NHS Trusts across the UK, co-led by Edinburgh with Nottingham, Dundee, Cambridge, Southampton, University College London and supported by six other centres (Belfast, Cardiff, Leeds, Leicester, Manchester and Royal Brompton).
For the first time ever, it will provide a single ‘go to’ centre that will connect children and adults with rare respiratory disease with clinical experts, researchers, investors and industry leaders across the UK. The £9.4M centre will create a UK-wide biobank of patient samples and models of disease that will allow researchers to advance pioneering therapies and engage with industry and regulatory partners to develop innovative human clinical studies.
Professor Marciniak said: “There are many rare lung diseases, and together those affected constitute a larger underserved group of patients. The National Translational Centre for Rare Respiratory Diseases brings together expertise from across the UK to find effective treatments and train the next generation of rare disease researchers.”
Former BBC News journalist and presenter, Philippa Thomas, has the rare incurable lung disease, Lymphangioleiomyomatosis (LAM). Her condition has stabilised but for many people, the disease can be severely life-limiting. Philippa said: “There is so little research funding for rare respiratory diseases, that getting treatment - let alone an accurate diagnosis - really does feel like a lottery. It is also terrifying being diagnosed with something your GP will never have heard of.”
Globally, there are more than 300 million people living with rare diseases. However, rare disease research can be fragmented. Researchers can lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management, which are vital in getting new innovations to patients.
Dr Catriona Crombie, Head of Rare Disease at LifeArc, says: “We’re extremely proud to be launching four new LifeArc Translational Centres for Rare Diseases. Each centre has been awarded funding because it holds real promise for delivering change for people living with rare diseases. These centres also have the potential to create a blueprint for accelerating improvements across other disease areas, including common diseases.”
Adapted from a press release from LifeArc
Cambridge researchers will play key roles in two new centres dedicated to developing improved tests, treatments and potentially cures for thousands of people living with rare medical conditions.
The new LifeArc centre unites scientific and clinical strengths from across the UKPatrick ChinneryAlexander_Safonov (Getty)Woman inhaling from a mask nebulizer
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Training AI models to answer ‘what if?’ questions could improve medical treatments
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 Michaela 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.
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.
Yuichiro Chino via Getty ImagesComputer-generated image of human brain
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Mess is best: disordered structure of battery-like devices improves performance
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.
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 ForseNathan PittLeft to right: Clare Grey, Xinyu Liu, Alex Forse
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Steven Barrett appointed Regius Professor of Engineering
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).
An expert on the environmental impacts of aviation, Barrett joins the University of Cambridge from MIT.
MITSteven Barrett
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Artificial Intelligence beats doctors in accurately assessing eye problems
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
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 ThirunavukarasuMavocado on Getty
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AI speeds up drug design for Parkinson’s ten-fold
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
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 Nathan PittMichele Vendruscolo
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Interspecies competition led to even more forms of ancient human – defying evolutionary trends in vertebrates
Climate has long been held responsible for the emergence and extinction of hominin species. In most vertebrates, however, interspecies competition is known to play an important role.
Now, research shows for the first time that competition was fundamental to “speciation” – the rate at which new species emerge – across five million years of hominin evolution.
The study, published today in Nature Ecology & Evolution, also suggests that the species formation pattern of our own lineage was closer to island-dwelling beetles than other mammals.
“We have been ignoring the way competition between species has shaped our own evolutionary tree,” said lead author Dr Laura van Holstein, a University of Cambridge biological anthropologist at Clare College. “The effect of climate on hominin species is only part of the story.”
In other vertebrates, species form to fill ecological “niches” says van Holstein. Take Darwin’s finches: some evolved large beaks for nut-cracking, while others evolved small beaks for feeding on certain insects. When each resource niche gets filled, competition kicks in, so no new finches emerge and extinctions take over.
Van Holstein used Bayesian modelling and phylogenetic analyses to show that, like other vertebrates, most hominin species formed when competition for resources or space were low.
“The pattern we see across many early hominins is similar to all other mammals. Speciation rates increase and then flatline, at which point extinction rates start to increase. This suggests that interspecies competition was a major evolutionary factor.”
However, when van Holstein analysed our own group, Homo, the findings were “bizarre”.
For the Homo lineage that led to modern humans, evolutionary patterns suggest that competition between species actually resulted in the appearance of even more new species – a complete reversal of the trend seen in almost all other vertebrates.
“The more species of Homo there were, the higher the rate of speciation. So when those niches got filled, something drove even more species to emerge. This is almost unparalleled in evolutionary science.”
The closest comparison she could find was in beetle species that live on islands, where contained ecosystems can produce unusual evolutionary trends.
“The patterns of evolution we see across species of Homo that led directly to modern humans is closer to those of island-dwelling beetles than other primates, or even any other mammal.”
Recent decades have seen the discovery of several new hominin species, from Australopithecus sediba to Homo floresiensis. Van Holstein created a new database of “occurrences” in the hominin fossil record: each time an example of a species was found and dated, around 385 in total.
Fossils can be an unreliable measure of species’ lifetimes. “The earliest fossil we find will not be the earliest members of a species,” said van Holstein.
“How well an organism fossilises depends on geology, and on climatic conditions: whether it is hot or dry or damp. With research efforts concentrated in certain parts of the world, and we might well have missed younger or older fossils of a species as a result.”
Van Holstein used data modelling to address this problem, and factor in likely numbers of each species at the beginning and end of their existence, as well as environmental factors on fossilisation, to generate new start and end dates for most known hominin species (17 in total).
She found that some species thought to have evolved through “anagenesis” – when one slowly turns into another, but lineage doesn’t split – may have actually “budded”: when a new species branches off from an existing one.*
This meant that several more hominin species than previously assumed were co-existing, and so possibly competing.
While early species of hominins, such as Paranthropus, probably evolved physiologically to expand their niche – adapting teeth to exploit new types of food, for example – the driver of the very different pattern in our own genus Homo may well have been technology.
“Adoption of stone tools or fire, or intensive hunting techniques, are extremely flexible behaviours. A species that can harness them can quickly carve out new niches, and doesn’t have to survive vast tracts of time while evolving new body plans,” said van Holstein
She argues that an ability to use technology to generalise, and rapidly go beyond ecological niches that force other species to compete for habitat and resources, may be behind the exponential increase in the number of Homo species detected by the latest study.
But it also led to Homo sapiens – the ultimate generalisers. And competition with an extremely flexible generalist in almost every ecological niche may be what contributed to the extinction of all other Homo species.
Added van Holstein: “These results show that, although it has been conventionally ignored, competition played an important role in human evolution overall. Perhaps most interestingly, in our own genus it played a role unlike that across any other vertebrate lineage known so far.”
Competition between species played a major role in the rise and fall of hominins, and produced a “bizarre” evolutionary pattern for the Homo lineage.
This is almost unparalleled in evolutionary scienceLaura van HolsteinThe Duckworth LaboratoryA cast of the skull of Homo Heidelbergensis, one of the hominin species analysed in the latest study.
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