̽��ֱ�� of Cambridge - Department of Clinical Neurosciences

Powerful new MRI scans enable life-changing surgery in first for adults with epilepsy

cjb250 — Fri, 21 Mar 2025 00:01:25 +0000

Scientists have developed a new technique that has enabled ultra-powerful MRI scanners to identify tiny differences in patients’ brains that cause treatment-resistant epilepsy. It has allowed doctors at Addenbrooke’s Hospital, Cambridge, to offer the patients surgery to cure their condition.

Cambridge and London hospitals to pioneer brain implants to combat alcohol and opioid addiction

cjb250 — Mon, 17 Mar 2025 08:00:50 +0000

̽��ֱ��technique – known as deep brain stimulation – is to be trialled at Addenbrooke’s Hospital, Cambridge, and King’s College Hospital, London. ̽��ֱ��team behind the Brain-PACER: Brain Pacemaker Addiction Control to End Relapse study will soon be recruiting individuals with severe alcohol or opioid addiction who are interested in taking part.

Deep brain stimulation (DBS) is a neurosurgical procedure that delivers ongoing stimulation to the brain. DBS acts as a brain pacemaker to normalise abnormal brain activity. It is well-tolerated, effective and widely used for neurological disorders and obsessive compulsive disorder.

Although there have been several proof-of-concept studies that suggest DBS is effective in addictions, Brain-PACER – a collaboration between the ̽��ֱ�� of Cambridge, Kings College London and the ̽��ֱ�� of Oxford – is the first major, multicentre study to use DBS to treat craving and relapse in severe addiction.

Chief Investigator Professor Valerie Voon, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, said: “While many people who experience alcohol or drug addiction can, with the right support, control their impulses, for some people, their addiction is so severe that no treatments are effective. Their addiction is hugely harmful to their health and wellbeing, to their relationships and their everyday lives.

“Initial evidence suggests that deep brain stimulation may be able to help these individuals manage their conditions. We’ve seen how effective it can be for other neurological disorders from Parkinson’s to OCD to depression. We want to see if it can also transform the lives of people with intractable alcohol and opioid addiction.”

̽��ֱ��primary aim of the Brain-PACER study is to assess the effects of DBS to treat alcohol and opioid addiction in a randomised controlled trial study. Its mission is twofold: to develop effective treatments for addiction and to understand the brain mechanisms that drive addiction disorders.

DBS is a neurosurgical treatment that involves implanting a slender electrode in the brain and a pacemaker under general anaesthesia. These electrodes deliver electrical impulses to modulate neural activity, which can help alleviate symptoms of various neurological and psychiatric disorders.

Keyoumars Ashkan, Professor of Neurosurgery at King’s College Hospital and the lead surgeon for the study, said: “Deep brain stimulation is a powerful surgical technique that can transform lives. It will be a major leap forward if we can show efficacy in this very difficult disease with huge burden to the patients and society.”

During surgery, thin electrodes are carefully placed in precise locations of the brain. These locations are chosen based on the condition being treated. For addiction, the electrodes are placed in areas involved in reward, motivation, and decision-making.

Harry Bulstrode, Honorary Consultant Neurosurgeon at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and Clinical Lecturer at the ̽��ֱ�� of Cambridge, said: "We see first-hand how deep brain stimulation surgery can be life-changing for patients with movement disorders such as Parkinson’s disease and essential tremor. Thanks to this trial, I am now hopeful that we can help patients and their families – who have often struggled for years – by targeting the parts of the brain linked to addiction."

Dr David Okai, Visiting Senior Lecturer from the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, added: “DBS is safe, reversible and adjustable, so it offers a flexible option for managing chronic conditions. We hope it will offer a lifeline to help improve the quality of life for patients whose treatment until now has been unsuccessful.”

Details on the trial, including criteria for participation, can be found on the Brain-PACER website.

̽��ֱ��research is supported by the Medical Research Council, UK Research & Innovation.

People suffering from severe alcohol and opioid addiction are to be offered a revolutionary new technique involving planting electrodes in the brain to modulate brain activity and cravings and improve self-control.

We’ve seen how effective deep brain stimulation can be for neurological disorders from Parkinson’s to OCD to depression. We want to see if it can also transform the lives of people with intractable alcohol and opioid addiction

Valerie Voon

Shamir R, Noecker A and McIntyre C

Graphic demonstrating deep brain stimulation

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

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Cambridge researcher aims to unlock new dementia treatments with nationwide blood test trial

sb726 — Thu, 13 Feb 2025 07:50:03 +0000

A simple blood test is being rolled out across the UK as part of a new study to detect early signs of dementia decades before it develops and help identify treatments.

Cambridge researchers developing brain implants for treating Parkinson’s disease

sc604 — Thu, 23 Jan 2025 10:33:21 +0000

As part of a £69 million funding programme supported by the Advanced Research + Invention Agency (ARIA), Professor George Malliaras from Cambridge’s Department of Engineering will co-lead a project that uses small clusters of brain cells called midbrain organoids to develop a new type of brain implant, which will be tested in animal models of Parkinson’s disease.

̽��ֱ��project led by Malliaras and Professor Roger Barker from the Department of Clinical Neurosciences, which involves colleagues from the ̽��ֱ�� of Oxford, the ̽��ֱ�� of Lund and BIOS Health, is one of 18 projects funded by ARIA as part of its Precision Neurotechnologies programme, which is supporting research teams across academia, non-profit R&D organisations, and startups dedicated to advancing brain-computer interface technologies.

̽��ֱ��programme will direct £69 million over four years to unlock new methods for interfacing with the human brain at the neural circuit level, to treat many of the most complex neurological and neuropsychiatric disorders, from Alzheimer’s to epilepsy to depression.

By addressing bottlenecks in funding and the lack of precision offered by current approaches, the outputs of this programme will pave the way for addressing a much broader range of conditions than ever before, significantly reducing the social and economic impact of brain disorders across the UK.

Parkinson’s disease occurs when the brain cells that make dopamine (a chemical that helps control movement) die off, causing movement problems and other symptoms. Current treatments, like dopamine-based drugs, work well early on, but can cause serious side effects over time.

In the UK, 130,000 people have Parkinson’s disease, and it costs affected families about £16,000 per year on average – more than £2 billion in the UK annually. As more people age, the number of cases will grow, and new treatments are urgently needed.

One idea is to replace the lost dopamine cells by transplanting new ones into the brain. But these cells need to connect properly to the brain’s network to fix the problem, and current methods don’t fully achieve that.

In the ARIA-funded project, Malliaras and his colleagues are working on a new approach using small clusters of brain cells called midbrain organoids. These will be placed in the right part of the brain in an animal model of Parkinson’s disease. They’ll also use advanced materials and electrical stimulation to help the new cells connect and rebuild the damaged pathways.

“Our ultimate goal is to create precise brain therapies that can restore normal brain function in people with Parkinson’s,” said Malliaras.

“To date, there’s been little serious investment into methodologies that interface precisely with the human brain, beyond ‘brute force’ approaches or highly invasive implants,” said ARIA Programme Director Jacques Carolan. “We’re showing that it’s possible to develop elegant means of understanding, identifying, and treating many of the most complex and devastating brain disorders. Ultimately, this could deliver transformative impact for people with lived experiences of brain disorders.”

Other teams funded by the programme include one at Imperial College London who is developing an entirely new class of biohybridised technology focused on engineering transplanted neurons with bioelectric components. A Glasgow-led team will build advanced neural robots for closed-loop neuromodulation, specifically targeting epilepsy treatment, while London-based Navira will develop a technology for delivering gene therapies across the blood-brain barrier, a crucial step towards developing safer and more effective treatments.

Adapted from an ARIA media release.

Cambridge researchers are developing implants that could help repair the brain pathways damaged by Parkinson’s disease.

Our ultimate goal is to create precise brain therapies that can restore normal brain function in people with Parkinson’s

George Malliaras

Science Photo Library via Getty Images

Substantia nigra in the human brain, illustration

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Ultra-powered MRI scans show damage to brain’s ‘control centre’ is behind long-lasting Covid-19 symptoms

sc604 — Tue, 08 Oct 2024 01:28:45 +0000

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford were able to observe the damaging effects Covid-19 can have on the brain.

̽��ֱ��study team scanned the brains of 30 people who had been admitted to hospital with severe Covid-19 early in the pandemic, before vaccines were available. ̽��ֱ��researchers found that Covid-19 infection damages the region of the brainstem associated with breathlessness, fatigue and anxiety.

̽��ֱ��powerful MRI scanners used for the study, known as 7-Tesla or 7T scanners, can measure inflammation in the brain. Their results, published in the journal Brain, will help scientists and clinicians understand the long-term effects of Covid-19 on the brain and the rest of the body. Although the study was started before the long-term effects of Covid were recognised, it will help to better understand this condition.

̽��ֱ��brainstem, which connects the brain to the spinal cord, is the control centre for many basic life functions and reflexes. Clusters of nerve cells in the brainstem, known as nuclei, regulate and process essential bodily functions such as breathing, heart rate, pain and blood pressure.

“Things happening in and around the brainstem are vital for quality of life, but it had been impossible to scan the inflammation of the brainstem nuclei in living people, because of their tiny size and difficult position.” said first author Dr Catarina Rua, from the Department of Clinical Neurosciences. “Usually, scientists only get a good look at the brainstem during post-mortem examinations.”

“ ̽��ֱ��brainstem is the critical junction box between our conscious selves and what is happening in our bodies,” said Professor James Rowe, also from the Department of Clinical Neurosciences, who co-led the research. “ ̽��ֱ��ability to see and understand how the brainstem changes in response to Covid-19 will help explain and treat the long-term effects more effectively.”

In the early days of the Covid-19 pandemic, before effective vaccines were available, post-mortem studies of patients who had died from severe Covid-19 infections showed changes in their brainstems, including inflammation. Many of these changes were thought to result from a post-infection immune response, rather than direct virus invasion of the brain.

“People who were very sick early in the pandemic showed long-lasting brain changes, likely caused by an immune response to the virus. But measuring that immune response is difficult in living people,” said Rowe. “Normal hospital-type MRI scanners can’t see inside the brain with the kind of chemical and physical detail we need.”

“But with 7T scanners, we can now measure these details. ̽��ֱ��active immune cells interfere with the ultra-high magnetic field, so that we’re able to detect how they are behaving,” said Rua. “Cambridge was special because we were able to scan even the sickest and infectious patients, early in the pandemic.”

Many of the patients admitted to hospital early in the pandemic reported fatigue, breathlessness and chest pain as troubling long-lasting symptoms. ̽��ֱ��researchers hypothesised these symptoms were in part the result of damage to key brainstem nuclei, damage which persists long after Covid-19 infection has passed.

̽��ֱ��researchers saw that multiple regions of the brainstem, in particular the medulla oblongata, pons and midbrain, showed abnormalities consistent with a neuroinflammatory response. ̽��ֱ��abnormalities appeared several weeks after hospital admission, and in regions of the brain responsible for controlling breathing.

“ ̽��ֱ��fact that we see abnormalities in the parts of the brain associated with breathing strongly suggests that long-lasting symptoms are an effect of inflammation in the brainstem following Covid-19 infection,” said Rua. “These effects are over and above the effects of age and gender, and are more pronounced in those who had had severe Covid-19.”

In addition to the physical effects of Covid-19, the 7T scanners provided evidence of some of the psychiatric effects of the disease. ̽��ֱ��brainstem monitors breathlessness, as well as fatigue and anxiety. “Mental health is intimately connected to brain health, and patients with the most marked immune response also showed higher levels of depression and anxiety,” said Rowe. “Changes in the brainstem caused by Covid-19 infection could also lead to poor mental health outcomes, because of the tight connection between physical and mental health.”

̽��ֱ��researchers say the results could aid in the understanding of other conditions associated with inflammation of the brainstem, like MS and dementia. ̽��ֱ��7T scanners could also be used to monitor the effectiveness of different treatments for brain diseases.

“This was an incredible collaboration, right at the peak of the pandemic, when testing was very difficult, and I was amazed how well the 7T scanners worked,” said Rua. “I was really impressed with how, in the heat of the moment, the collaboration between lots of different researchers came together so effectively.”

̽��ֱ��research was supported in part by the NIHR Cambridge Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, and the ̽��ֱ�� of Oxford COVID Medical Sciences Division Rapid Response Fund.

Reference:
Catarina Rua et al. ‘7-Tesla quantitative susceptibility mapping in COVID-19: brainstem effects and outcome associations.’ Brain (2024). DOI: 10.1093/brain/awae215

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

̽��ֱ�� of Cambridge

3D projections of QSM maps on the rendered brainstem

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One in four patients in vegetative or minimally conscious state able to perform cognitive tasks, study finds

cjb250 — Wed, 14 Aug 2024 21:00:11 +0000

Severe brain injury can leave individuals unable to respond to commands physically, but in some cases they are still able to activate areas of the brain that would ordinarily play a role in movement. This phenomenon is known as ‘cognitive motor dissociation’.

To determine what proportion of patients in so-called ‘disorders of consciousness’ experience this phenomenon – and help inform clinical practice – researchers across Europe and North America recruited a total of 353 adults with disorders of consciousness, including the largest cohort of 100 patients studied at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust.

Participants had mostly sustained brain injury from severe trauma, strokes or interrupted oxygen supply to the brain after heart attacks. Most were living in specialised long-term care facilities and a few were living at home with extensive care packages. ̽��ֱ��median time from injury for the whole group was about eight months.

Researchers assessed patterns of brain activation among these patients using functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). Subjects were asked to repeatedly imagine performing a motor activity (for example, “keep wiggling your toes”, “swinging your arm as if playing tennis”, “walking around your house from room to room”) for periods of 15 to 30 seconds separated by equal periods of rest. To be able to follow such instructions requires not only the understanding of and response to a simple spoken command, but also more complex thought processes including paying attention and remembering the command.

̽��ֱ��results of the study are published today in the New England Journal of Medicine.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge said: “When a patient has sustained a severe brain injury, there are very important, and often difficult, decisions to be made by doctors and family members about their care. It’s vitally important that we are able to understand the extent to which their cognitive processes are still functioning by utilising all available technology.”

Among the 241 patients with a prolonged disorder of consciousness, who could not make any visible responses to bedside commands, one in four (25%) was able to perform cognitive tasks, producing the same patterns of brain activity recorded with EEG and/or fMRI that are seen in healthy subjects in response to the same instructions.

In the 112 patients who did demonstrate some motor responses to spoken commands at the bedside, 38% performed these complex cognitive tasks during fMRI or EEG. However, the majority of these patients (62%) did not demonstrate such brain activation. This counter-intuitive finding emphasises that the fMRI and EEG tasks require patients to have complex cognitive abilities such as short-term memory and sustained concentration, which are not required to the same extent for following bedside commands.

These findings are clinically very important for the assessment and management of the estimated 1,000 to 8,000 individuals in the UK in the vegetative state and 20,000 to 50,000 in a minimally conscious state. ̽��ֱ��detection of cognitive motor dissociation has been associated with more rapid recovery and better outcomes one year post injury, although the majority of such patients will remain significantly disabled, albeit with some making remarkable recoveries.

Dr Judith Allanson, Consultant in Neurorehabilitation, said: “A quarter of the patients who have been diagnosed as in a vegetative or minimally conscious state after detailed behavioural assessments by experienced clinicians, have been found to be able to imagine carrying out complex activities when specifically asked to. This sobering fact suggests that some seemingly unconscious patients may be aware and possibly capable of significant participation in rehabilitation and communication with the support of appropriate technology.

“Just knowing that a patient has this ability to respond cognitively is a game changer in terms of the degree of engagement of caregivers and family members, referrals for specialist rehabilitation and best interest discussions about the continuation of life sustaining treatments.”

̽��ֱ��researchers caution that care must be taken to ensure the findings are not misrepresented, pointing out, for example, that a negative fMRI/EEG result does not per se exclude cognitive motor dissociation as even some healthy volunteers do not show these responses.

Professor John Pickard, emeritus professorial Fellow of St Catharine's College, Cambridge, said: “Only positive results – in other words, where patients are able to perform complex cognitive processes – should be used to inform management of patients, which will require meticulous follow up involving specialist rehabilitation services.”

̽��ֱ��team is calling for a network of research platforms to be established in the UK to enable multicentre studies to examine mechanisms of recovery, develop easier methods of assessment than task-based fMRI/EEG, and to design novel interventions to enhance recovery including drugs, brain stimulation and brain-computer interfaces.

̽��ֱ��research reported here was primarily funded by the James S. McDonnell Foundation. ̽��ֱ��work in Cambridge was supported by the National Institute for Health and Care Research UK, MRC, Smith’s Charity, Evelyn Trust, CLAHRC ARC fellowship and the Stephen Erskine Fellowship (Queens’ College).

Reference
Bodien, YG et al. Cognitive Motor Dissociation in Disorders of Consciousness. NEJM; 14 Aug 2024; DOI: 10.1056/NEJMoa2400645

Adapted from a press release from Weill Cornell Medicine

Around one in four patients with severe brain injury who cannot move or speak – because they are in a prolonged coma, vegetative or minimally conscious state – is still able to perform complex mental tasks, a major international study has concluded in confirmation of much smaller previous studies.

When a patient has sustained a severe brain injury, there are very important, and often difficult, decisions to be made by doctors and family members about their care

Emmanuel Stamatakis

Witthaya Prasongsin (Getty Images)

Male patient in a hospital bed - stock image

Acknowledgements

̽��ֱ��multidisciplinary Cambridge Impaired Consciousness Research Group, led by Emeritus Professors John Pickard (Neurosurgery) & David Menon (Anaesthesia) and Drs Judith Allanson & Emmanuel A. Stamatakis (Lead, Cognition and Consciousness Imaging Group), started its research programme in 1997, partly in response to emerging concern over the misdiagnosis of the vegetative state. This pioneering work has only been possible by having access to the world class resources of the Wolfson Brain Imaging Centre, the NIHR/Wellcome Clinical Research Facility at Addenbrooke’s Hospital, the MRC Cognition and Brain Sciences Unit (Professors Barbara Wilson & Adrian Owen), the Royal Hospital for Neuro-disability (Putney) and the Central England Rehabilitation Unit (Royal Leamington Spa).

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Advanced MRI scans help identify one in three concussion patients with ‘hidden disease’

cjb250 — Thu, 08 Aug 2024 22:30:10 +0000

Around one in 200 people in Europe every year will suffer concussion. In the UK, more than 1 million people attend Emergency Departments annually with a recent head injury. It is the most common form of brain injury worldwide.

When a patient in the UK presents at an Emergency Department with head injury, they are assessed according to the NICE head injury guidelines. Depending on their symptoms, they may be referred for a CT scan, which looks for brain injuries including bruising, bleeding and swelling.

However, CT scans identify abnormalities in fewer than one in 10 patients with concussion, yet 30-40% of patients discharged from the Emergency Department following a scan experience significant symptoms that can last for years and be potentially life-changing. These include severe fatigue, poor memory, headaches, and mental health issues (including anxiety, depression, and post-traumatic stress).

Dr Virginia Newcombe from the Department of Medicine at the ̽��ֱ�� of Cambridge and an Intensive Care Medicine and Emergency Physician at Addenbrooke’s Hospital, Cambridge, said: “ ̽��ֱ��majority of head injury patients are sent home with a piece of paper telling them the symptoms of post-concussion to look out for and are told to seek help from their GP if their symptoms worsen.

“ ̽��ֱ��problem is that the nature of concussion means patients and their GPs often don’t recognise that their symptoms are serious enough to need follow-up. Patients describe it as a ‘hidden disease’, unlike, say, breaking a bone. Without objective evidence of a brain injury, such as a scan, these patients often feel that their symptoms are dismissed or ignored when they seek help.”

In a study published today in eClinicalMedicine, Dr Newcombe and colleagues show that an advanced form of MRI known as diffusion tensor imaging (DTI) can substantially improve existing prognostic models for patients with concussion who have been given a normal CT brain.

DTI measures how water molecules move in tissue, providing detailed images of the pathways, known as white matter tracts, that connect different parts of the brain. Standard MRI scanners can be adapted to measure this data, which can be used to calculate a DTI ‘score’ based on the number of different brain regions with abnormalities.

Dr Newcombe and colleagues studied data from more than 1,000 patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study between December 2014 and December 2017. 38% of the patients had an incomplete recovery, meaning that three months after discharge their symptoms were still persisting.

̽��ֱ��team assigned DTI scores to the 153 patients who had received a DTI scan. This significantly improved the accuracy of the prognosis – whereas the current clinical model would correctly predict in 69 cases out of 100 that a patient would have a poorer outcome, DTI increased this to 82 cases out of 100.

dti_images_web.jpg

Whole brain diffusion tensor tractography showing healthy patient (left) and patient at two days (centre) and six weeks (right) after severe traumatic brain injury (Credit: Virginia Newcombe)

̽��ֱ��researchers also looked at blood biomarkers – proteins released into the blood as a result of head injury – to see whether any of these could improve the accuracy of the prognosis. Although the biomarkers alone were not sufficient, concentrations of two particular proteins – glial fibrillary acidic protein (GFAP) within the first 12 hours and neurofilament light (NFL) between 12 and 24 hours following injury – were useful in identifying those patients who might benefit from a DTI scan.

Dr Newcombe said: “Concussion is the number one neurological condition to affect adults, but health services don’t have the resources to routinely bring back every patient for a follow-up, which is why we need a way of identifying those patients at greatest risk of persistent symptoms.

“Current methods for assessing an individual’s outlook following head injury are not good enough, but using DTI – which, in theory, should be possible for any centre with an MRI scanner – can help us make much more accurate assessments. Given that symptoms of concussion can have a significant impact on an individual’s life, this is urgently needed.”

̽��ֱ��team plan to look in greater details at blood biomarkers, to see if they can identify new ways to provide even simpler, more practical predictors. They will also be exploring ways to bring DTI into clinical practice.

Dr Sophie Richter, a NIHR Clinical Lecturer in Emergency Medicine and first author, Cambridge, added: “We want to see if there is a way to integrate the different types of information obtained when a patient presents at hospital with brain injury – symptoms assessment, blood tests and brain scans, for example – to improve our assessment of a patient’s injury and prognosis.”

̽��ֱ��research was funded by European Union's Seventh Framework Programme, Wellcome and the National Institute for Health and Care Excellence.

Reference
Richter, S et al. Predicting recovery in patients with mild traumatic brain injury and a normal CT using serum biomarkers and diffusion tensor imaging (CENTER-TBI): an observational cohort study. eClinMed; 8 Aug 2024; DOI: 10.1016/j.eclinm.2024.102751

Offering patients with concussion a type of brain scan known as diffusion tensor imaging MRI could help identify the one in three people who will experience persistent symptoms that can be life changing, say Cambridge researchers.

Concussion is the number one neurological condition to affect adults, which is why we need a way of identifying those patients at greatest risk of persistent symptoms

Virginia Newcombe

Callista Images (Getty Images)

Diffusion tensor imaging (DTI) MRI of the human brain - stock photo

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Cambridge scientists elected as Members of the European Molecular Biology Organisation

jg533 — Tue, 09 Jul 2024 12:00:56 +0000

Five Cambridge researchers join the community of over 2,100 leading life scientists today as the European Molecular Biology Organisation (EMBO) announces its newest Members in its 60th anniversary year.