The awards are part of a major round of funding under the Clinical Research Infrastructure Initiative, announced today by the Chancellor of the Exchequer, George Osborne. The Initiative will bring together funding from UK Government, devolved administrations, Arthritis Research UK, British Heart Foundation, the Wellcome Trust and Cancer Research UK, to advance clinical research in 23 key projects at centres across the country, including research teams at fifteen universities.

Speaking at the launch, Chancellor Osborne said: “The UK is already a world leader in science and research, which is why at Budget, I protected science spending. Today we go a step further by announcing £150 million of new investment in clinical research infrastructure. The funding will go to 23 truly innovative projects from across the UK today that represent the best of British ingenuity and scientific exploration. The Government, charities, universities and industry will be working together to advance our knowledge in combatting the biggest medical challenges of our time.”

Patrick Maxwell, Regius Professor at the University of Cambridge’s School of Clinical Medicine, says: “Advances in medical research and technology provide us with opportunities to make real differences to the diagnosis and treatment of patients. This significant funding will enable us to utilise some of the most innovative and cutting-edge approaches to clinical research at the University of Cambridge, ensuring that we remain one of the world leaders in this field.”

The funding to the University of Cambridge is across three themes. The first will focus on stratified medicine. Many diseases are traditionally diagnosed and treated as if all patients with the same diagnosis were largely the same, such as breast cancer, but advances in biomedical science are increasingly demonstrating that there are in fact many different genetic and molecular pathways to the same clinical diagnosis. This has potentially important implications for more precise targeting of treatment: more refined diagnostic stratification of patients could identify more exactly which patients were most likely to respond to specific treatments.

To enable the increased stratification of diseases, the University will create three new high-tech facilities for clinical research: a Stratified Medicine Core Laboratory, a Molecular Imaging Centre, and a High Performance Hub for Informatics. The facilities will provide innovative ways of diagnosing and stratifying patients, with immediate implications for the patients’ care, as well as providing the infrastructure to manage the increasingly massive amounts of data generated by such research.

The second theme focuses on the use of next generation Magnetic Resonance Imaging (MRI) to study dementia, mental health and neuroscience. Conventional MRI has revolutionised the study of the brain over the last twenty years, but the scanners have their limitations. The MRC award will allow researchers to procure an ultrahigh-field (7 Tesla) MRI scanner, which offers a major step forward in how clearly one can study the brain's structure, function and chemistry, allowing researchers to understand how the brain works as a whole while still seeing detail at a sub-millimetre scale.

The scanner will be installed on the Cambridge Biomedical Campus, next to Addenbrooke’s Hospital, and is a collaboration between the University of Cambridge and the MRC's Cognition and Brain Sciences Unit, working closely with the NHS. It will be a major contributor to the UK Dementia Platform, a unique and radical approach to join up medical research across the country's specialist centres and drug company partners in the fight against dementia.

In addition, the funding will enable the procurement of additional imaging equipment including a PET-MRI scanner and a new clinical hyperpolariser, as well as upgrading existing MRI scanners.

The third theme will focus on examining diseases at single cell resolution, building on recent developments in technology that have revolutionised our ability to characterize, quantify and isolate single cells. Examination of diseases at single cell resolution, both at diagnosis and after treatment, will transform the practice of molecular medicine by improving the quality of patient diagnosis, refining treatment options, monitoring the response to treatment, and detecting the emergence of resistance to treatment. Cambridge scientists have been at the forefront of basic research in single cell expression profiling and the analysis of circulating tumour DNA, as well as setting up local biotech ‘spinout’ companies that develop novel single cell technologies.

The MRC funding will enable the creation of the Cambridge Single Cell Analysis Clinical Core Facility, a new shared core facility for single cell analysis that will serve all major molecular medicine programmes in Cambridge: cancer, neurosciences, immunity and inflammation, infectious diseases, stem cell and regenerative medicine, metabolic medicine and experimental therapeutics. The facility will work closely with strategic partners in the Cambridge area such as the Babraham Institute, Wellcome Trust Sanger Institute, the European Bioinformatics Institute, the MRC Laboratory for Molecular Biology and major pharmaceutical and biotechnology companies to bring their different capabilities to bear on clinical research challenges.

Amy Li was born in China but attended school in the UK, and won a place to study Chemical Engineering at Emmanuel College, Cambridge. 

After graduating in 2010 she took up a post as safety engineer with DNV GL, a leading organization in the maritime, oil and gas, and energy industries.  She died only three years later, whilst working in Aberdeen.

Her colleagues at DNV GL determined to remember her by establishing a scholarship that will enable international students to follow in her footsteps at Cambridge.

The first recipient of the Amy Li Scholarship is Jiaqi Liu (pictured central with Helen Pennant, of the Cambridge Trust right, and Lorraine Headen, Senior Associate Director, Principal Gifts).

Jiaqi, from North Eastern China,  who won her scholarship to attend boarding school in the UK, has just started her BA in Mathematics at Newnham College. She said she was honoured to become the very first Amy Li scholar at Cambridge.

"Coming to Cambridge has been a long-held dream of mine and this scholarship has enabled me to do this. It sounds like Amy was an amazing person and I am happy that we can remember her in this way ."

The scholarship is jointly funded by the donation from DNV GL and by an award from the Cambridge Commonwealth, European & International Trust, which exists to support outstanding international students at the University.

The scholarships will be awarded to undergraduates from any country outside the EU, and will be available to outstanding applicants in Mathematics, Physics, Engineering or Chemical Engineering.

Selected scholars will benefit from interaction with the staff of DNV GL, including possible summer vacation placements.

Dr Patrick Barrie, Director of Teaching in the Department of Chemical Engineering and Biotechnology, was Amy Li's Director of Studies while she was at Cambridge. He said “I remember interviewing Amy for admission and supervising her.  I was deeply saddened by the tragic news of her death last year at such an early stage of her life and career. The establishment of these scholarships, aimed at helping students like Amy, mean that her name will be remembered.”

Gary Tomlin, Vice-President for Safety and Risk at DNV GL, said: “Amy had an outstanding attitude, charisma and spirit for everything she did, both at work and in her own leisure time.”

In the 2001 Census, 0.7% of the UK population - some 390,127 - declared themselves Jedi: the mystical religion from legendary film franchise Star Wars. This was a result of a viral online campaign to ridicule, or ‘troll’, the Census, which had dared to ask the religion question for the first time in living memory.

Ten years later, the digital gag apparently on the wane, less than half that number self-selected as a Jedi - although the 2011 number was not insignificant. There are allegedly 176, 632 Jedis in the UK.

The Office of National Statistics coded Jedi under ‘no religion’, seeing it simply as an atheistic prank. For most, this is likely accurate. But a minority do, in fact, practise Jediism - a spiritual and religious philosophy that, while looking to Star Wars as the primary source text, is developing in its own right through online communities of believers.

Beth Singler, a researcher at the University’s Faculty of Divinity, is a digital anthropologist studying new religious movements. She says that social media and digital networks allow practicing Jedis to formulate their observances, doctrine and ritual beyond the parameters originally laid out by Star Wars creator George Lucas, filling in gaps and negotiating the directions of this emerging faith - a faith in which they find meaning.

“Jedis see it as an aspirational religion, a positively-aimed system,” she said. “It’s not entirely worked out within the Star Wars universe, so Jedis are creating their own texts referring to Daoism, Buddhism, and Catholicism even. They are working out the master/apprentice system the films provided, and how that’s navigated online when the master is in Texas and the apprentice in Bavaria.

“The Jedi community talk about the role of George Lucas as a storyteller who appropriated ideas from different places and by merging them in Jediism formed a kind of truth - a truth they can pick up and run with. At points, the line between fandom and religion becomes quite diffuse.”

For Singler, Jediism is one of a number of new religious movements and spiritualities such as Scientology, Wicca and the Indigo Children that are using digital platforms to create new traditions and build communities. Part of the attraction of these ‘invented religions’ and spiritualities is being involved in the establishment of a belief system and, as arguably with all religions, acceptance from a community of like-minded believers. 

Singler says that these new religions increasingly use the digital world to map religious development, providing new sources of tradition that movements can reference to ‘prove’ themselves and the legitimacy of their faith. This raises a question as old as religion itself: what actually constitutes a religion? Do you need centuries of power and devotion, or a number of people with a common belief?

Singler describes herself as, in a sense, the “anti-Dawkins”. While the furiously atheist Professor Dawkins believes all religion to be irrational, for Singler, religious movements are all “equally rational”.

“As a social anthropologist, I’m not debating the truth of belief or whether there’s a god. Once you bracket that question off, one is left with social manifestations; I would say the social manifestations of religions throughout time are equally rational: responses to hopes and expectations, social pressures and changes. Emergent spiritual forms are just the repetition of previous ways of making sense of the world.”

Singler estimates a vocal Jedi community to be roughly 2,000 strong in the UK, not much smaller than the Census figure for Scientology, the new religious movement that has fought hardest for what it sees as official ‘legitimacy’: waging a decades-long struggle with a number of governments to be given the tax-exempt charitable status afforded major religions. 

The Jedi themselves were mentioned in a proposed amendment during the drafting of the UK’s Racial and Religious Hatred Act 2005 (“we have to face up to the fact that Jedi Knights seemed to feature in the census return as being the belief of rather a large number of people”). Again this raised the thorny issue of what is and is not a religion, described by one MP as going to the “heart of the Bill”. In the end, the Bill side-stepped the issue with a vagueness that caused consternation among satirists, who feared they would face prosecution under the Act for being deemed offensive.

For her research, Singler follows online debates, pulls at threads and scours Facebook groups - conducting interviews both on and offline. As someone raised with the internet, she says objectivity is critical: “It’s not like the traditional mode of anthropology where you join remote tribal communities; it can be easy to assume that people are using language in the same way as you, and are similar to you. It’s an increasing problem as ethnography shifts into digital.”

One of the new formations Singler focuses on are the Indigo Children. Part of the broader New Age movement, Indigos were first identified by psychic Nancy Ann Tappe in the late 70s. Tappe saw a new generation of children born with different colour auras who would be the harbingers of a new age of spiritual enlightenment. For Singler, the idea that a special generation of people are here to save us is a trope that everyone from medieval historians (the Children’s Crusade) to comic book fans (X-Men) will find familiar.

Part of the belief system for Indigo Children is that they are here to break paradigms, and don’t fit well into mainstream society. Indigos will often demedicalise conditions such as ADHD and Autism - seeing them more as manifestations of the disruptive characteristics of these individuals. The Indigo Child concept allows people to reinterpret personal histories (“this is why I didn’t fit in”) and ascribe the religion to historical figures (“Joan of Arc is considered by some to be an ‘Indigo’”).   

Using Twitter to research Indigos, Singler found hallmarks of this belief system in a perhaps unlikely cultural space: hip-hop. “There is a whole thread of Indigoism going on in hip-hop, specifically the experimental Brooklyn-based movement Beast Coast. For these artists, Indigo thinking is a part of the human potential movement that ties into things like the 1%er culture and the Nation of Islam. Lyrics reflect new age ideas such as ‘the third eye’, ‘awakening to the truth’ and not being ‘sheeple’, or unawaken.” Beast Coast figureheads The Underachievers titled their debut release ‘Indigoism’.

While this idea of self-awareness in religious observance might seem to be a fairly new practice, one amplified by digital technology, Singler isn’t sure. She points to Victorian spiritualism as an example of another boom period of new religious movements - and one influenced by different technologies. “The Fox sisters were one of the key triggers for the spiritualism movements in the mid-19th century. They were the first to interpret rapping noises as channelled spirit messages from beyond - at the same time the telegraph system was sweeping the western world.”

However, Singler admits that the internet allows new religious movements to get more publicity, and provides an enabling space. Even the Wicca, with its nostalgia for the rural, pagan and ancient, are far from luddites when it comes to new technology:

“Wiccans were early adopters of many social media channels - and remain very active. Many are vocal online campaigners for environmental issues. There are even online witch schools, for example, with regular time slots to log in for sessions and rituals.”  

But Singler insists she is not a ‘technological determinist’. “Yes, the digital world allows collectivity, but the internet doesn’t create us, we create the internet and then it becomes a new space for us to continue being what we’ve always been. The formation of new religious movements is far from a new phenomenon, it’s just humans being humans.”

Beth Singler will be giving a public talk about her research as part of this year's Festival of Ideas on Saturday 25 October.

Inset image: Yoga Auras by A4gpa

In individuals living in the Arctic, researchers have discovered a genetic variant that arose thousands of years ago and most likely provided an evolutionary advantage for processing high-fat diets or for surviving in a cold environment; however, the variant also seems to increase the risk of hypoglycemia, or low blood sugar, and infant mortality in today’s northern populations.

The findings, published online in the American Journal of Human Genetics, provide an example of how an initially beneficial genetic change could be detrimental to future generations.

“Our work describes a case where the same variant has likely been selectively advantageous in the past [but] disadvantageous under current environmental conditions,” said senior author Dr. Toomas Kivisild, from the University of Cambridge's Division of Biological Anthropology.

Kivisild and his colleagues analyzed the genomes of 25 individuals from Northern Siberia and compared their sequences with those from 25 people from Europe and 11 from East Asia.

The team identified a variant that was unique to Northern Siberians and was located within CPT1A, a gene that encodes an enzyme involved in the digestion of long fatty acids, which are prevalent in meat-based diets. With agriculture being unsustainable in Arctic regions as a result of the extremely cold environment, coastal populations there have historically fed mostly on marine mammals.

When the investigators looked at the global distribution of the CPT1A variant, they found that it was present in 68% of individuals in the Northern Siberian population yet absent in other publicly available genomes. The variant has previously been linked to high infant mortality and hypoglycemia in Canadian Inuits, and its high frequency in these populations has been described as a paradox.

“The study’s results illustrate the medical importance of having an evolutionary understanding of our past and suggest that evolutionary impacts on health might be more prevalent than currently appreciated,” said lead author Dr. Florian Clemente, also from the Division of Biological Anthropology.

Story from Cell Press.

The scans of the two historic mannequins were taken at Addenbrooke's Hospital, part of Cambridge University Hospitals, to discover their internal workings without damaging them.  At the same time, radiologists and engineers were able to use the data from the non-human bodies to test not yet clinically approved software on the images, furthering research for potential clinical practice in the future.

The procedure was led by radiologist Dr Tom Turmezei.  He said: “The mannequins contain both natural materials and worked metals, making for an interesting human analogue.  Humans are getting more and more artificial metal parts in their bodies, for example in joint replacements, clips and plates.  When these are scanned with the CT machine it creates a starburst effect in the final image, called an artifact, and this bright white flare-like trace obscures details in the surrounding tissue.  Clinically this can be a big problem as it can make it difficult to perceive both damage to the metal part and any disease in the tissue around it, such as an abscess, blood clot or tumour.  As we are moving towards more metallic, electronic and even robotic body parts, being able to reduce the artifact in the scan is ever more important.”

Metal Deletion Technique software from Revision Radiology was used on the scans to look at the effectiveness of the algorithm to reduce the artifact.

The two mannequins scanned were ‘Child no. 98’, a high quality 19th century Parisian stuffed lay figure from the Hamilton Kerr Institute, and an 18th century, largely wooden mannequin once belonging to Walter Sickert (1860-1942) from Bath Spa University.

Alongside the mannequins scanned at Addenbrooke’s, the public event on 28 October will tell the fascinating stories of two more historic figures: a 68cm tall figure from the Museum of London once belonging to the sculptor Louis-François Roubiliac (1695-1762) which was scanned separately to reveal an internal ‘skeleton’ made of saying iron, bronze and brass ; and how three specialists restored a 19th century figure belonging to the artist Alan Beeton (1880-1942) which had tattered fingers and a broken nose, this included a textile conservator, a modeller of medical prosthetics and a sculptress specialising in papier mâché.

Artist’s mannequins, although fascinating objects, were tools to be used in the studio: as such their history was not always rigorously documented, and today there are gaps in our knowledge about their exact manufacture.  The Addenbrooke’s CT scans also allowed documentation of their construction in detail, and uncovered hidden damages to the internal workings of the figures over time.  A fractured left knee joint in the Bath Spa mannequin was noted so the object can now be moved safely in the future.

Dr Turmezei continued: “Above all, the purpose of doing these scans was art historical; to discover their material composition and construction in a non-invasive way and confirm suspicions art historians had about these objects.  Looking at these mannequins you can see the incredible drive to create a more accurate model of the human body and the developments that happened to allow this to take place.  The Bath Spa model is mostly wood, by the time Child no. 98 was made they had moved to a wooden skeleton and metal joinery, padded out with horse hair and hessian.  A great deal of effort was taken to give Child no. 98 as accurate anatomy as possible: the body has padding inside for flank and abdominal muscles, there is padded material inside the chest to make lungs, a belly button and even glass beads under the chest ‘skin’ for nipples.”

The collaboration on the scans is part of a continuing relationship between Addenbrooke’s Hospital and art institutions in the region, including ongoing displays of art for patients and visitors and the recent Quentin Blake commissions for the Hospital.

The story of the four mannequins will be discussed in detail at a Curating Cambridge festival event at the Fitzwilliam Museum on 28 October, Mannequins with x-ray vision, which will explore how makers strove to produce the 'perfected' mannequin to serve the artist's every need.  The event is part of the exhibition Silent Partners: Artist and Mannequin from Function to Fetish at the Fitzwilliam Museum until 25 January 2015.

Inset images: A 68cm tall figure from the Museum of London once belonging to the sculptor Louis-François Roubiliac (1695-1762) which was scanned to reveal an internal ‘skeleton’ made of saying iron, bronze and brass. Credit: Fitzwilliam Museum

The team of researchers, led by Dr Rafael Carazo Salas from the Department of Genetics, combined high-resolution 3D confocal microscopy and computer-automated analysis of the images to survey the fission yeast genome with respect to three key cellular processes simultaneously: cell shape, microtubule organisation and cell cycle progression. Microtubules are small, tube-like structures which help cells divide and give them their structure.

Of the 262 genes whose functions the team report in a study published today in the journal Developmental Cell, two-thirds are linked to these processes for the first time and a third are implicated in multiple processes.

“More than ten years since the publication of the human genome, the so-called ‘Book of Life’, we still have no direct evidence of the function played by half the genes across all species whose genomes have been sequenced,” explains Dr Carazo Salas. “We have no ‘catalogue’ of genes involved in cellular processes and their functions, yet these processes are fundamental to life. Understanding them better could eventually open up new avenues of research for medicines which target these processes, such as chemotherapy drugs.”

Using a multi-disciplinary strategy that took the team over four years to develop, the researchers were able to manipulate a single gene at a time in the fission yeast genome and see simultaneously how this affected the three cellular processes. Fission yeast is used as a model organism as it is a unicellular organism – in other words, it consists of just one cell – whereas most organisms are multicellular, yet many of its most fundamental genes carry out the same function in humans, for example in cell development.

The technique enabled the researchers not only to identify the functions of hundreds of genes across the genome, but also, for the first time, to systematically ask how the processes might be linked. For example, they found in the yeast – and, importantly, validated in human cells – a previously unknown link between control of microtubule stability and the machinery that repairs damage to DNA. Many conventional cancer therapies target microtubular stability or DNA damage, and whilst there is evidence in the scientific literature that drugs targeting both processes might interact, the reason why has been unclear.

“Both the technique and the data it produces are likely to be a very valuable resource to the scientific community in the future,” adds Dr Carazo Salas. “It allows us to shine a light into the black box of the genome and learn exciting new information about the basic building blocks of life and the complex ways in which they interact.”

All the data from the study is being published online as an open resource for researchers to use. It will be available online at www.sysgro.org.

The research was largely funded by the European Research Council, the Swiss Initiative in Systems Biology and the Swiss National Foundation.

Human stem cell research is a thriving field of science worldwide – holding promise for treating diseases such as diabetes, multiple sclerosis and Parkinson’s disease, as well as for furthering our understanding of how we develop from the very earliest stages of life.

But using human embryonic stem (ES) cells to improve the health of other humans has also been the subject of comment, criticism and even court cases. Time magazine dubbed the “complexity and drama” surrounding these cells as the “Great Debate”.

Most notably, the field witnessed the 2001 restriction on funding for ES cell research in the USA by President Bush and the lifting of the ban in 2009 by President Obama. Then in 2011, the Court of Justice of the European Union (CJEU) banned the patenting of inventions derived from human eggs or their equivalent on the basis that they were human embryos, the commercial exploitation of which “would be contrary to… morality.”

While religious bodies and green lobbyists use patent law to elevate the status of the embryo, scientists argue that doing so threatens research that might benefit the health of millions.

International law permits states to refuse patents where necessary to protect morality in their territory. “Yet, how does a patent examiner or a court assess whether an invention is immoral to the point that, unlike other inventions, it can’t be patented? That is a particularly difficult question,” said Dr Kathy Liddell from the Faculty of Law. “It is a conundrum that runs headlong into the complex intersection of law and morality, intellectual property and philosophy.”

It is precisely this intersection that a new research centre in the Faculty will investigate. The new centre – funded by the Hatton Trust and the WYNG Foundation – will focus on medical law, ethics and policy relating to controversial issues such as patenting inventions involving DNA and body parts, the regulation of medical research and technologies, assisted reproduction and surrogacy, and the governance of ‘big data’ in the medical field, as well as the regulatory and legislative issues that stem cell research is likely to meet en route from the lab to the clinic.

“These areas need to be considered not as a post hoc rationalisation of events that have already happened, but alongside and ahead of technological advances,” said Liddell, who is centrally involved in the new centre, as well as being Deputy Director of the Faculty’s Centre for Intellectual Property and Law. “To complement the extraordinary science that is happening, we need to consider the ramifications of biomedical advances in a thorough and timely way.”

Liddell’s own research interests relate to the pathway that leads from the research bench to clinically effective treatments. She sees the law’s role as facilitating and supporting this pathway in morally responsible ways.

ES cells are useful because they are at the earliest point of human development and possess the full ‘regenerative toolkit’. In other words, they can develop into any type of cell in the human body. Although stem cells found in the adult human also retain the self-renewing ability to develop into specific tissues, they cannot develop into all the tissue types needed for regenerative medicine; the genetic information needed for some developmental pathways has already been shut down.

“The CJEU was very reluctant to engage with the ethical and public policy debates surrounding human embryos. So it ended up answering the patent law questions with very little reasoning,” added Liddell.

“For me, this was the biggest problem with the judgment. The Court has to have the courage, skills, wisdom and accountability to face up to the degree of judicial activism and policy shaping that is inevitable in these controversial areas. Likewise, citizens, researchers and NGOs have to accept that judges have to make difficult ‘calls’ in the face of moral and scientific uncertainty. They simply can’t please everyone in a morally pluralist society.”

Julian Hitchcock, a specialist in life science intellectual property at London law firm Lawford Davies Denoon, who advises government and the Wellcome Trust on stem cell law, agrees: “The problem I see is that the CJEU’s decision sends the message that scientists engaged in stem cell research are immoral. Moreover, the CJEU’s decision is being used to attempt wider assaults on research, such as in a Citizens’ Initiative called ‘One of Us’ which suggested that the principle of human dignity applies from the point of conception. Had this initiative succeeded, not only would it have undermined research funding, but it would also have impeded the fulfilment of urgent Millennium Development Goals.”

Meanwhile, the great stem cell debate continues, with a recent challenge in the High Court by the International Stem Cell Corporation over a decision by the Patent Office that unfertilised human eggs that have been stimulated to divide (turning them into so-called parthenotes) be included in the term ‘human embryos’. The implication is that parthenote inventions would also fall within the CJEU’s zone of unpatentable inventions. The High Court referred the issue to the CJEU and, in July this year, the Court was advised to reject part of the decision by the Advocate General.

“It’s a very complex area of the law – both highly technical and highly controversial. By supporting people to develop expertise in the life sciences and the law, we can better respond to these important discussions,” said Liddell.

Hitchcock added: “Formulating laws and policies that are responsive to the needs of research, and which carry the support of the public, requires a deep understanding of the ways that biology and law intersect, as well as imaginative thinking, powerful advocacy and the courage to fight an often embattled corner.”

“The quintessential justification for patent protection has always been that it’s important for protecting investment in research and commercialisation,” said Liddell.

“We have yet to see whether the lack of patent protection for inventions involving human embryos has had a chilling effect on the transition of ideas to clinical realities, or whether it has nudged research in new, but similarly effective, directions that avoid the moral dilemmas and legal uncertainties of using embryos. We may never know – it is very difficult to gather this sort of empirical data. But for society to benefit properly and fully from medical advances, we do know that we need to be ready to enter any and all debates that wrestle with their ethical and moral implications.”

Inset images: Human embryonic stem cells via Wikimedia; Dr Kathy Liddell

Just before implantation in the uterus, the ball of cells, called a blastocyst, gains the capacity to generate all of the cell types of the subsequent adult – a feature called pluripotency. It is at this moment when everything is possible, when the history of the previous generation has been wiped clean and when the embryo begins its unique course of development.

But, although these ‘naive’ stem cells have been isolated in mice – and mouse cells at a later stage of development can be manipulated to take them back to full naivety – the same has not been convincingly accomplished for humans.

In fact, in an assessment earlier this year, Cambridge researchers Professor Roger Pedersen and PhD student Victoria Mascetti concluded that the existence of naive human stem cells required confirmation by other stem cell research groups: “Like Higgs’ Boson to the field of particle physics,” they explained, naivety in human stem cells “was predicted from considerations of symmetry and conservation, [but] we are yet to unlock its potential."

Now researchers led by the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute have managed to induce a ground state by rewiring the genetic circuitry in human embryonic stem (ES) cells and in adult cells that have been induced into a pluripotent state. Their ‘reset cells’ share many of the characteristics of authentic naive ES cells isolated from mice, suggesting that they represent the earliest stage of development.

“Capturing ES cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues,” explained Professor Austin Smith, Director of the Institute, who co-authored a recent paper on the research. “Scientists have perfected a reliable way of doing this with mouse cells, but human cells have proved more difficult to arrest. They show subtle differences between the individual cells. It’s as if the developmental clock has not stopped at the same time and some cells are a few minutes ahead of the others.”

He added: “Truly naive human ES cell lines would not only help answer fundamental questions about how we are made, and be useful for drug screening and tissue therapy, but they would also provide a benchmark against which other types of stem cells could be measured in terms of their effectiveness in stem cell therapy and regenerative medicine.”

Over the past 20 years, research groups led by Smith and Dr Jenny Nichols at the Institute have made a major contribution both to understanding the early stages of mouse development and to determining how to make stable mouse stem cell lines more efficiently. They know enough to realise that it’s very different in humans, as Nichols explained: “Pluripotent cells that seem very similar to the mouse naive pluripotent cells appear in the human blastocyst before implantation but we don’t know what happens to those cells for the following week of development. We can only make assumptions based on what happens in the mouse.”

Their recent study, published in September 2014 in the journal Cell, proves that they are closer to capturing naive pluripotency in humans: “We know almost all we need to know about the molecular requirements for creating the ground state in mice,” Smith said. “We have identified the genes and growth factors involved and, thanks to a collaboration with Microsoft Research, we can now computationally model the control circuitry in mouse cells. It’s reinforced our view that we understand enough to know what to look for in humans and which combinations of  genes to focus on. It’s now only a matter of time.”

And when that happens, work will begin on comparing them with other sources of stem cells, through collaborations such as the PluriMes project that Smith coordinates, a newly launched consortium of 10 European partners focused on directing pluripotent stem cells to become bone and muscle, and a collaboration with orthopaedic surgeon Professor Andrew McCaskie (see panel).

Could naive human ES cells be the stem cell of choice for tissue therapy? “We don’t yet know,” said Smith. “These cells would offer the hope of having a broader and more consistent ability to differentiate into a range of cell types because they are at an earlier stage of development. But it’s also entirely possible that current stem cells are good enough for some applications. The point is, we needed these new stem cells in order to find out what is best.”

Inset image: Austin Smith and Jenny Nichols

In 1780 a group of gypsies was hung in Northampton and their supporters threatened to set the town alight. Nothing is known about the crime for which the gypsies died or, indeed, if there was one. A law passed in 1562 had made it illegal even to be a gypsy (‘those calling themselves Egyptians’) and throughout history the poor with no fixed abode or occupation had been, at best, viewed with deep suspicion. However, the ‘Egyptians Act’ was finally repealed in 1783. Four years later, a German writer called Heinrich Grellmann published the first taxonomy of gypsies which documented “the Manner of Life, Economy, Customs and Conditions of these people in Europe, and their origin”. The book caused a surge of public interest in what a gypsy might be.

These three events, which marked the beginning of a shift in the narratives surrounding one of society’s most marginalised groups, provide a powerful backdrop to the topics explored in Representations of the Gypsy in the Romantic Period by Dr Sarah Houghton-Walker, a lecturer in English at Gonville & Caius College, Cambridge. The book, published today (30 October 2014) by Oxford University Press, treads new territory in its analysis of portrayals of travellers and wanderers in literature between 1783 and 1832. Its author touches on work by well-known poets and novelists – including John Clare, William Cowper, William Wordsworth, George Eliot, Jane Austen, Henry Fielding and Charlotte Bronte – as well as literature once popular but now largely forgotten.

Notable among the more obscure works is the wickedly titled The Life and Adventures of Bampfylde-Moore Carew, the Noted Devonshire Stroler and Dog-Stealer, a biography of an adventurer and rogue thought to have been written by a Dorset printer. First published in 1749, and repeatedly republished when it became a best seller, the book tells the (highly improbable) story of a well-born young man who runs away from school to live with a band of vagabonds whose bounteous fun and freedom he is unable to resist.

The book describes Carew’s first encounter with these merry-makers: “…after a plentiful Meal upon Fowls, Ducks, and other dainty Dishes, the flowing Cups of October, Cyder, &c. went most chearfully round, and merry Songs and Country Dances crowned the jovial Banquet: In short, so great an Air of Freedom, Mirth and Pleasure, appeared in the Faces and Gestures of this Society, that our Youngster from that Time conceived a sudden Inclination to enlist into their Company; which, when they communicated to the Gypsies, they considering their Appearance, Behaviour and Education, regarded as spoken only in jest.” From these beginnings, Carew rose to be self-styled ‘King of the Gypsies’.

‘Gypsy’ is today a contested term with modern communities favouring alternatives such as Romani and Traveller. It is, however, the word used by the writers whose work Houghton-Walker discusses and one that she therefore adheres to. In her study, the word ‘gypsy’ refers to an idea or a phenomenon as much as it does to any figures who might have existed – and its connotations in the period that Houghton-Walker considers are both positive and negative, much as they are today.

In her examination of how writers represented gypsies, Houghton-Walker brings to light a number of literary interactions that confound expectations. The politically radical Wordsworth, whose love of the Lakes was profoundly influential on the literary production of the period, reveals a conflicted response to the gypsies he encounters. His poem ‘Gipsies’ depicts them as lazy whereas, as the wandering poet, he portrays himself as a more valuable kind of "traveller under an open sky". The poem, it has been argued, reflects Wordsworth’s own anxiety about being an idle wanderer with no ‘proper job’.

The conservative novelist Austen, on the other hand, constructs a much more sympathetic picture in a chance meeting between Harriet Smith, Frank Churchill and a group of gypsies that creates a moment of crisis and crux in the plot of Emma. The gypsies camped on a verge in Highbury are not straightforwardly nasty, dirty thieves and their threat is seen to lie only in the over-active imagination of silly young women. Perhaps counterintuitively, Austen seems to suggest that despite their reputation for criminality, the gypsies have a place in English society and must therefore be accommodated within it.

Perhaps Houghton-Walker’s most striking discovery in researching the book was the description of an encounter between Princess (later Queen) Victoria and a group of gypsies. The princess records in her diary for Christmas Day 1836 that her mother had ordered broth, fuel and blankets, as well as a worsted knit baby jacket, to be taken to the gypsy family. The diary reveals the Princess’s compassion for the “poor wanderers” who are “the chief ornament of the Portsmouth Road” – and “a nice set of Gipsies… not at all forward or importunate, and so grateful”.

It’s no coincidence that the gypsies Princess Victoria met in Epsom were half-starved. The half century covered by Houghton-Walker’s study was a time of rapid social and economic change in both town and country as the growing population put pressure on all kinds of resources. The open commons, wide verges and uncultivated heathlands that had long afforded space for encampments of gypsies and grazing for their animals, were increasingly being enclosed.

Growing industrialisation saw the loss of traditional and seasonal tasks that previously had provided an income for groups of travellers. Clare’s poems show gypsies interacting closely with the day-to-day life of the village, mending chairs and playing the fiddle. At the same time, the belief systems practised by the rural poor, including travellers, were changing, with the old customs pushed out by the sceptical empiricism of the enlightenment, just as reforming evangelical Christians brought their own pressures to bear on the gypsies’ way of life.  

Representations of the Gypsy stems from Houghton-Walker’s preoccupation with walking and verse, and her fascination with the way in which metrical feet seem to interact with human ones. Her work on Clare, in particular, prompted her to consider the broader theme of wandering and the ways in which the figure of the gypsy embodies anxieties about identity and questions about Englishness. As wanderers, whose presence is often not discovered until they have moved on, gypsies are repeatedly figured in the Romantic period as fascinating and feared, familiar yet exotic, known and unknown. They thus provide a lens through which questions about what is and isn’t understood can be focused.

“The Romantic period marks the moment when, after a long stretch of being classed as foreigners and outsiders, gypsies find a new place in the English rural landscape. They are shown to be deeply conservative in their loyalty to old-fashioned ways, and in their resistance to any change at all while, at the same time, representing a brand of radicalism that’s both troubling and seductive for writers,” said Houghton-Walker.

“We’re talking about a period that saw a significant change in attitudes to people who were wanderers. Unless you were a member of the local community, if you turned up on foot at an inn in the 18^th century, you would be suspected of nefarious motives. No-one walked unless they had to. Towards the end of the century, however, walking became a fashionable pursuit. Wordsworth, who may have walked around 180,000 miles in his lifetime, contributed to this vogue for travel on foot. Walking was newly understood as a means of encountering and responding to landscapes.”

In a chapter devoted to representations of the gypsy by artists of the Romantic period, Houghton-Walker focuses on the painters Thomas Gainsborough and George Morland. The work of both artists can be seen to engage with subtle class differences within the context of the English landscape. “In Morland’s painting ‘Morning, or the Benevolent Sportsman’, we witness the stereotypes attached to gypsies – they sit on the cold earth, sheltered only by a rough structure, while the sportsman sits astride his horse - but also a particular kind of defence of gypsies on the part of the artist,” said Houghton-Walker.

“Morland’s gypsies challenge conventions. The young man boldly returns the rider’s gaze and there’s little deference evident in the group around the tent. What’s striking is the contrast between the gypsy and the bagman (the sportsman’s servant). The almost Messianic light emanating from the sportsman’s horse illuminates the gypsy camp while the bagman is cast into darkness. But, through the composition of the painting, Morland shows us that the gun the bagman holds still matters. The ‘benevolent sportsman’ is the temporary identity of a man who pays this same servant to shoot at gypsies.”

In Bronte’s Jane Eyre, published in 1847 but set earlier in the 19^th century, Mr Rochester dresses as a gypsy to tell Jane’s fortune and therefore reveal truths that will move the plot onwards. Jane is taken in by his disguise and speeches. Yet by this point in literary history, a profound shift has taken place in the representation of gypsies.  Houghton-Walker said: “By the 1830s, the gypsy in literature has become merely a piece of theatre – a mask that can be picked up or put down on a whim. Tamed now, and owned by the cultural imagination in new ways, the figure of the gypsy abandons its sublimity and becomes instead the figure of cultural conservatism that the Victorian age was to draw on and delight in.”

Representations of the Gypsy in the Romantic Period by Sarah Houghton-Walker is published by Oxford University Press on 30 October 2014

Putting a price on the services which a particular ecosystem provides may encourage the adoption of greener policies, but it may come at the price of biodiversity conservation. Writing today (30 October) in the journal Science, Professor Bill Adams of the University’s Department of Geography argues that assigning a quantitative value to nature does not automatically lead to the conservation of biodiversity, and may in fact contribute to species loss and conflict.

While assigning a monetary value to the benefits of an ecosystem can be an essential tool in the environmental planning process, unequal access to those benefits, particularly where there are differences in wealth and power, can lead to poor trade-offs being made, both for the ecosystem itself and those who rely on it.

“Putting a price on what nature provides is not in itself a conservation measure,” said Adams. “There is a risk that traditional conservation strategies oriented toward biodiversity may not be effective at protecting the economic benefits of an ecosystem, and vice-versa.”

For example, when stream channels in the US state of Maryland were re-engineered to provide a means of natural flood control, it ended up causing the loss of trees which had been growing next to the water and were unable to adapt to their new, drier environment.

The ways in which we depend on our natural environment are increasingly expressed as ‘ecosystem services’, or the range of benefits we get from nature for free. These benefits include the provision of food and clean water, erosion control and carbon storage. Quantifying the value of nature in this way is meant to allow policymakers to consider the potential economic and social impacts of altering a particular habitat.

This approach does sometimes lead to win-win scenarios, where the value of ecosystem services is dependent upon a high level of biodiversity. One example is in the coffee plantations of Costa Rica, where the retention of forest habitat in areas around the plantations doubled the amount of pest control of coffee berry borer beetle provided by birds, which benefitted the coffee farmers while protecting biodiversity.

However, consideration of ecosystem services when making decisions does not automatically lead to retention of biodiversity. “In many cases, trade-offs are made,” said Adams.

Several factors cause tension between biodiversity conservation and ecosystem services. One problem is that the biological and physical processes that guarantee the supply of specific ecosystem services may be different from those that support valued species. An ecosystem that is managed to deliver particular services may not support particular elements of biodiversity.

A second problem is that there are often no markets for some vital services, such as soil formation and nutrient cycling, and while payment schemes can be created to create market-like structures, the value assigned to ecosystem services depends on market prices, which are subject to change. 

A third problem arises from the institutional and political processes linking economic benefits from ecosystems and human wellbeing. “Unequal access to benefits, for example where there are differences in wealth and power among stakeholders, can lead to trade-offs being made, with negative impacts for the ecosystem itself and those who rely on it,” Adams comments “It’s not enough to identify the net benefits of ecosystem services; it also matters who gets them.”

For example, in Nepal, research has shown that forests managed by the local community, rather than by the state, yielded benefits of clean water, tourism and harvested wild goods. However, these forests restricted poorer people’s access to forest-derived products, creating hardship, illegal use and impacts on other areas.

“In a world run according to economic arguments, the survival of biotic diversity will depend on its price,” said Adams. “Sometimes economics will favour conservation and sometimes it won’t. But conservationists need to plan for both outcomes.”

It sounds like something from a 1950s’ B-movie: scientists growing brains in the lab. It brings to mind images of dimly lit, cobweb-filled rooms with brains pulsating in glass tanks.

The truth, of course, is far less gothic. The Wellcome Trust/Cancer Research UK Gurdon Institute, where the research is taking place, is light, airy and hi-tech. But although Dr Rick Livesey, who leads the study, does not like to call them ‘mini-brains’, that is in essence what they are: clusters of millions of nerve cells, electrically active and networked to each other, and no bigger than a freckle. What makes these ‘brains’ particularly useful is that they are diseased – they have Alzheimer’s.

Almost 40 million people worldwide are living with Alzheimer’s disease, and as more people live into old age, this number is set to rise. For a disease first described in 1906, surprisingly little is understood about its mechanisms, and there are no treatment options to prevent or reverse its progress. We do know, however, that the disease is characterised by the build-up in the brain of two types of protein: beta-amyloid, which clumps together into ‘plaques’, and tau, which accumulates in nerve cells to form ‘tangles’. These proteins disrupt the behaviour of the nerve cells, which lose their connections and eventually die.

The standard way to study a disease is to use animals. Crudely speaking, you insert a human disease gene or series of genes into a mouse and observe the mechanisms that lead the animal to develop the disease. This approach is useful for asking specific questions, but doesn’t show the disease process in a cohesive way. It can lead to the development of drugs that treat the disease in mice but fail when it comes  to humans.

Instead, Livesey has turned to stem cells, building on research that won Sir John Gurdon, the man who gave his name to the institute at which Livesey now works, a Nobel Prize in 2012.

Most people who develop Alzheimer’s begin showing symptoms in later life, from their sixties onwards. However, a small number of people – less than 1% of cases – have a genetic form of the disease that runs in their families, caused by a single change in one of three genes. If you carry the mutation, you will get Alzheimer’s – and onset is typically in one’s thirties or forties.

Livesey takes skin cells from patients with this familial form of Alzheimer’s and reprogrammes them to become induced pluripotent stem cells, which resemble embryonic stem cells, with the ability to turn into almost any type of cell in the body. By guiding them to develop as neural stem cells, which create the brain’s nerve cells, he makes two-dimensional clusters of nerve cells that model the cerebral cortex, the area of the brain that is affected by Alzheimer’s. These clusters connect to each other, forming circuits – essential for modelling early stages of Alzheimer’s, which affects the ability of neurons to communicate with each other. It’s a very labour-intensive – and fraught – process that takes months. “We grow them in a sugar and salt mixture, and what do bacteria love but sugar and salt! You’re always paranoid you’re going to lose them,” explained Livesey.

These clusters allow the researchers to replay a disease process that takes 30 or 40 years but over three or four months. In humans, our immune system does its best to fight off the disease, but eventually this clearance mechanism gets overwhelmed. “In the dish, these specialist clearance cells, called microglia, are absent so the disease process is faster. One of the beauties of our models is that we can add microglia and see what the effect of the immune system is and if we can use it to make things better or worse.”

As well as allowing Livesey to study the fundamental biology of the disease, his mini-brains are powerful tools for screening potential drug candidates. To use animals for this purpose would mean using tens of thousands of mice which, as Livesey points out, “would be both impractical and ethically indefensible.” Livesey puts the clusters into all 96 wells of a plate the size of a mobile phone and adds a different compound to each well. “We do this every two days for a month, monitoring to see if the disease gets better. We might try different doses of the same compound – we say well look, this is fine with whacking great amounts, but will it ever work as a real drug at concentrations suitable for humans?”

Thanks to a recent £2 million award from Alzheimer’s Research UK, Livesey, together with colleagues at University College London, has also begun work on modelling more common forms of the disease. These share the same pathology as the familial forms, but may arise through fundamentally different mechanisms. “We know there is some overlap between the two forms, but there’s a risk that we develop a treatment for familial Alzheimer’s which won’t work in the general population if the disease doesn’t start in the same way.”

The research does, however, pose an interesting ethical question: when is a model of a brain actually human? Livesey’s models are made up of human cells and have many of the properties of real brains, but they cannot learn, do not think and are not sentient – they are not ‘human’ in that sense. “All of the nerve cells we make are excitatory – they’re like ‘on’ switches. Real brains also have a second, inhibitory nerve cell type, which acts like an ‘off’ switch and modulates the neural circuits. These add an extra layer of complexity which is missing in our models.

“But honestly, we simply don’t understand the cellular basis for sentience, let alone consciousness, so we probably wouldn’t know it if we saw it. Nor are we clear whether it’s a scale or a complexity issue. Our neural clusters are tiny, only around a million nerve cells, whereas a real brain has about 86 billion. If we made it big enough, say a kilogram, would it become a human brain? Probably not, as we’re not capturing all the complexity of the system. So what if the brain model was smaller, but captured all the complexity, like a mouse brain – would that cause ethical concerns? It’s a question we cannot ignore as we move forward. But we’re still a long way off there yet.”

Inset image: Rick Livesey

New research shows that graduates who went to private schools earn substantially more than those who went to state schools. Even amongst graduates who went to the same university to study the same subject and who left with the same degree class, those who attended private school earned on average 7% more.

Previous work by the researchers found that graduates who attended private schools are more likely to enter higher status and higher paying occupations. But, once they matched occupations in the comparison fields for the latest research, latest research showed that those who went to a private school still earn 6% more, on average, than those who went to a state school. This is currently equivalent to around £1,500 a year.

The findings suggest that even when universities widen participation to students from poor backgrounds, there are social inequalities in the success of graduates when they leave higher education.

The new study, published recently by the Institute for Fiscal Studies, and funded by the Nuffield Foundation, concludes that further research is needed to determine the causes behind the pay gap - whether it is access to particular social networks or better non-cognitive skills such as confidence or self-esteem. Regardless of the explanation, the authors suggest that these results add further weight to the argument that higher education is not the great leveller it was hoped to be. 

“Whilst universities have been making strenuous efforts to widen participation in recent years, what happens after students leave their university is also enormously important for their prospects for social mobility. If higher education is to be a  route to social mobility then  the link between family background and adult outcomes must be broken, or at least reduced, for graduates,” said study co-author Professor Anna Vignoles, from Cambridge’s Faculty of Education.

“These results suggest that there is a pressing need to understand why private schooling confers such an advantage in the labour market, even amongst similarly achieving graduates.”

Researchers used longitudinal samples from the Destination of Leavers from Higher Education survey to look at gross annual earnings six months after graduation, with a sample of 75,000 graduates and for a subset of these they looked at earnings three and a half years after graduation.

The researchers found that after six months the graduates who attended private school earned an average of £3,000 more than their state school contemporaries. They then looked at the earnings of graduates who left university in 2007 in January 2011, approximately three and a half years later. After this time the gap had increased, with former private school pupils earning an average of £4,500 more than those who attended a state school - amounting to a pay gap of roughly 17%.  

Arguably this might be expected, say the researchers, as some of the higher earnings of graduates who attended private schools is down to the fact that they have better A-level grades and this in turn enables them to go on to attend more prestigious universities and study subjects which tend to be more highly rewarded.

But once the researchers analysed graduates who went to the same university to study the same subject and who left with the same degree class, those who went to private schools still earn an average of 7% more three and a half years after graduation.

Amongst graduates from the same backgrounds, who studied the same subject in the same university, and who went into the same occupation, those from private schools still earn 6% more, on average, than those from state schools.

“Our research shows that, even amongst those who succeed in obtaining a degree, family background – and in particular the type of school they went to – continues to influence their success in the work place,” said co-author Dr Claire Crawford, from the University of Warwick’s Department of Economics.

Implicit within government policies to achieve social mobility through improving school and university results is the assumption that once a person has graduated from university, their family background and the school they went to will cease to impact on how much they earn, say the study’s authors, writing for the website The Conversation.

“But our new research proves that there is actually a strong relationship between the kind of schools graduates attended and their success in the labour market. Future research might usefully focus on why the influence of family background lingers long beyond graduation,” they write.