Features

Elephants living near Timbuktu make an annual journey encompassing an area of 32,000 square kilometres in order to find the food and water they need to survive.

The trek, made by a species of desert-adapted African elephant [Loxodonta Africana] from Mali's Gourma region, is the largest known elephant range anywhere in the world.

Nine individual animals were tracked by satellite using GPS collars by a team from Save the Elephants, University of British Columbia, and Oxford University, with their findings recently reported in the journal Biological Conservation.

One of the surprises from the research was that male and female elephants only shared a quarter of their ranges, possibly because females tend to be warier of humans or because they are looking for different types of vegetation.

'It's incredible these elephants have survived. They have a truly stressful life with the lack of water and food, and their giant range reflects that,' said Jake Wall of Save the Elephants, Kenya and the University of British Columbia, lead author of the study.

Yet the greatest threat to Gourma's elephants may be man not their harsh environment: three elephants from the region were killed by poachers this year.

'The Mali elephants with their record breaking migration have maintained their numbers in extreme natural conditions of heat and drought. We now fear that they may become victims of civil disturbance in the North of Mali due to the uprising currently taking place,' said Iain Douglas-Hamilton of Oxford University's Department of Zoology, Founder of Save The Elephants.

He added that a new anti-poaching initiative by the WILD foundation and the International Conservation Fund of Canada was beginning to engage local communities and national foresters in defence of elephants. The success of the scheme is all that stands between the poachers and their prey.

Over 13,000 years ago a stalagmite began to grow in a cave in Oregon.

Each winter rainwater from the land above made its way through the cave's ceiling and dripped onto the floor. As each layer of the stalagmite formed, oxygen and carbon isotopes within these raindrops were captured and preserved inside the rock. 

Now, thousands of years later, a team led by Oxford University scientists is using the data locked inside this stalagmite to get a glimpse of the ancient winter climate of Western North America. 

The team's results, published this week in Nature Communications, show that in recent prehistory the region has seen rapid shifts between dry and warm and wet and cold periods. The findings hint at the importance of the Pacific Decadal Oscillation [PDO] – a pattern of climate variability that changes every 50-70 years – to this area.

'We picked Oregon because it's around this latitude where winter storms hit the West coast of North America, it is representative for an area stretching from California to British Columbia,' Vasile Ersek of Oxford University's Department of Earth Sciences, lead author of the report, told me. Water resources in the region are highly dependent on winter rainfall, without the winter rains the land is arid. 

'Most other ways of estimating past climate, like tree ring data, only tell us about summers, when plants are growing,' Vasile explains. 'This work gives us a unique insight into winter climate over thousands of years with an unprecedented combination of length, detail and dating accuracy.

'Moreover, because the cave is only around 70 km from the Pacific Ocean, and directly affected by processes occurring over the ocean, it also represents a record of past climate variability in the Eastern Pacific where detailed records of past climate are otherwise very hard to obtain.'

The stalagmite record suggests that there have been important variations in both rainfall and temperature (c.1 degree Celsius) over the last 13,000 years – with the region's climate switching between extreme dry-warm and wet-cold periods within just a few decades. 

'Whilst we can't directly relate these changes to the Pacific Decadal Oscillation the mechanisms involved do look similar,' comments Vasile. 'Getting a long-term perspective on these sorts of natural climate variations may help us to understand the potential for future loss of winter snow cover along the west coast, as well as what’s happening out in the Pacific to influence other cyclical climate events such as El Niño.'

But those hoping that this cave rock might tell us about man's influence on the climate will be disappointed; after bearing witness to so many winters its record-keeping stopped before the industrial age began.

Above: the stalagmite that recorded 13,000 winters.

A report of the research, entitled ‘Holocene winter climate variability in mid-latitude western North America’, is published in Nature Communications.

A vaccine to protect children against meningitis B – the strain that now causes the vast majority of bacterial meningitis cases in this country – could soon be introduced in the UK.

On Friday the European Medicines Agency (EMA) recommended Novartis' Bexsero (MenB) vaccine for approval for babies 2 months and up. The step paves the way for a Europe-wide licence for the vaccine, and for national governments to decide whether to include it in childhood immunisation programmes.

'As paediatricians we have seen the devastating effect that MenB disease can have on young children and adolescents, so welcome the recommendation for approval for this vaccine as an important step towards the prevention of childhood meningitis,' says Dr Matthew Snape of the Oxford Vaccine Group, who is hopeful that the vaccine can be introduced into the routine immunisation schedule in the near future.

Oxford researchers, including Matthew Snape, Professor Andrew Pollard, Professor Moxon and others, played a significant role in the almost 20 years of work behind the development of the Novartis vaccine, from the early stages to clinical trials, as our earlier news story reported.

Matthew takes up the story: 'Developing a vaccine against MenB infections has been very difficult primarily because, unlike the MenC organism [a strain for which a successful vaccine was introduced in 1999], the outer coating of MenB is not recognised by the immune system.

'Over several decades many different proteins had been studied as vaccine targets without success. To overcome this, Professor Richard Moxon and others developed a novel approach whereby the MenB bacterium's DNA blueprint was used as a tool to find new protein targets,' says Matthew. 'This vaccine is a direct result of this work. It represents an entirely new approach to vaccine development, and one that has important implications for developing vaccines against other diseases.'

Professor Moxon of the Department of Paediatrics at Oxford University explains: 'The story of the underpinning science goes back to 1995. This is when the first complete genome sequence of the bacterium Haemophilus influenzae was completed and published.'

This advance opened up the possibility of using the sequenced genomes of other disease-causing bacteria as a new approach to making vaccines, as Richard later outlined in the Lancet. After all, a complete genome sequence would provide an inventory of all the genes encoding every factor responsible for the virulence of the disease, or that would prompt an immune response in the body. Vaccines that target one or more of these genes could then be developed.

'There already was a H. influenzae (type b) vaccine, so an obvious candidate for using a genomic approach was Neisseria meningitidis (meningococcus),' says Richard, 'and specifically the B strain, since for technical reasons a vaccine for this strain needed a completely new approach from that used for the ultimately successful MenC vaccine.'

Oxford had been one of the main collaborators on the project to sequence the entire DNA of H. influenzae, Richard explains, and he was then in position to persuade Craig Venter – the US scientist pioneering novel DNA sequencing methods at his private research institution, The Institute for Genomic Research – to consider sequencing meningococcus B.

Richard's laboratory in the Department of Paediatrics sent DNA from a B strain of meningococcus to Venter's group at TIGR in 1995. The strain was one isolated from an outbreak of meningitis in Stroud in 1981. Richard explains that some preliminary sequencing work began to demonstrate how powerful the genomic approach could be. At this stage, Rino Rappuoli, lead scientist at Chiron Vaccines in Italy, came in with serious project funding and, crucially, all the resources of a commercial vaccine development company. The result was a collaboration, initiated in 1996, between Chiron (later acquired by Novartis), Oxford University and TIGR in Maryland USA.

'Between 1996 and 2000, the sequencing and analysis of the B strain was carried out and culminated in two back-to-back papers in Science,' says Richard. 'The second of these papers identified a number of candidate vaccine antigens which, after much further research led by Mariagrazia Pizza at Novartis, culminated in formulations that went into clinical trials.

'The Oxford Vaccine Group was a huge player in the clinical trials that resulted in the decision by EMA,' says Richard.

The Oxford Vaccine Group, also in the Department of Paediatrics, has been involved in 7 different clinical trials of the MenB vaccine, enrolling a total of over 1000 participants (over 800 children and more than 250 students). These included the first studies in children which were performed in 2006.

Professor Andrew Pollard, head of the Oxford Vaccine Group and Matthew have been closely involved in the design, planning and analysis of results for these studies.

Matthew says: 'The initial paediatric studies conducted in 2006 enrolled 2 month old and 6 month old children to receive one of two formulations of this vaccine. One of these formulations induced a broad immune response against multiple strains of the MenB bacterium, and was therefore taken forward for further assessment in a larger study conducted across five European countries.'

The results from this larger study, in which the Oxford Vaccine Group was again involved, enrolling 400 of the 1800 infant participants, provided data critical to determining how the MenB vaccine might be incorporated into existing child immunisation schedules.

So what can we expect from the new MenB vaccine now it's on its way to being licensed? After all the meningitis C vaccine has been enormously successful. There have been only 2 deaths in children and young people under 20 in the last 5 years, compared to 78 deaths in the single year before the vaccine was introduced.

Matthew says: 'Each year between 460 and 860 children and adolescents suffer either meningitis or septicaemia (blood poisoning) due to MenB in England and Wales, with the highest rates being in children below 2 years of age.

'Calculating what proportion of these cases are likely to be prevented by immunisation with the MenB vaccine has been a considerable challenge, as the proteins targeted by the MenB vaccine vary between different MenB bacteria. But early estimates are in the region of 75%, which would be an enormous step forward in the goal of preventing childhood meningitis.'

He adds: 'As with all new vaccines, ongoing surveillance is going to be the key to understanding how the vaccine can be employed most effectively. One key question is whether using the vaccine in a large proportion of the population will reduce circulation of the organism in the community, thus providing "herd immunity" to people who have not received the vaccine.'

Many animals travel long distances in groups but little is known about how this may influence the navigational skills of individuals.

To test if travelling with others who know the way affects a bird's path-finding abilities a team from Oxford University, UCL, and Microsoft Research Cambridge, studied homing pigeons. They paired up experienced and less experienced - 'passenger' - pigeons on repeated flights and then recorded how well the birds navigated on their own.

I asked Benjamin Pettit of Oxford University's Department of Zoology, one of the authors of a report of the research in Proceedings of the Royal Society B, all about passengers, pigeons, and learning in a flock…

OxSciBlog: How might some animals be 'passengers' & others 'drivers'?
Benjamin Pettit: Animals that live in groups will often use each others' behaviour as a source of information - about food or predators, for example. This also applies to navigation.

In a travelling group, such as a migrating flock of birds, there will often be differences in experience, especially if animals of different ages have travelled the route a different number of times. Simulations of flocks suggest that only a minority need to know the way to guide the flock to its destination, so it is possible that only some of a flock is navigating, and the rest follow.

This raises the question of whether the 'passengers' in the group learn to navigate for themselves. Simply travelling with others who know the way already, like passengers in a car, could inhibit an individual’s route learning, making it harder to travel alone in the future. This has been called a 'passenger/driver' effect.

OSB: How did you examine the passenger/driver effect in pigeons?
BP: We track homing pigeons with mini GPS loggers. Over the past decade scientists have discovered a great deal about how a pigeon learns a route as it becomes more familiar with an area of the landscape.

In this experiment we compared route learning in two conditions - some pigeons flew alone, whereas others flew together with a trained 'demonstrator' pigeon, which had already learned a route home from that release site.

After a sequence of 12 flights, we tested the birds on their own. If being a 'passenger' interferes with learning, we would expect the birds trained in pairs to have more erratic routes when they then fly without the 'demonstrator'.

OSB: What does your study tells us about how pigeons share/gain information about a route?
BP: In fact, the birds trained in pairs learned homing routes just as well as if they had flown alone. This shows that a pigeon continues to pay attention to the landscape even if it has another pigeon to follow. The 'demonstrator' pigeons improved their homing routes as well, which was surprising.

In previous experiments, pigeons with this amount of experience settled into a particular homing route and rarely changed it. So rather than a homing route being strictly transferred from one bird to another, the pairs' routes ended up including new shortcuts that may have been discovered by the less experienced bird.

OSB: How might less experienced birds navigating benefit a flock?
BP: Birds can use a number of different cues to navigate over unfamiliar terrain, including geomagnetism, smells carried by the wind, and the position of the sun (or stars). So a bird over unfamiliar terrain is still likely to have some information to add to the flock's route choice. Theoretically, a flock can improve its navigational accuracy by combining information from as many birds as possible.

OSB: What further work is needed to examine route learning behaviour?
BP: Similar learning processes could be at work in flocks of migratory birds that travel in mixed-experience groups. This can be investigated through long-term tracking studies of wild birds, both species that migrate alone and those that form flocks. As for the pigeons, we already have plans to test how learning plays out in larger flocks. In particular, we will test whether a follower learns as quickly as leader, within a large flock.

This video [see below] was put together as part of a set of webpages that provide a great showcase of Oxford's research on the world's most pressing health problems in the parts of the globe where it matters most. It's life-changing research that perhaps we don’t celebrate enough.

After all, Oxford's global health programme got special mention as the university retained its crown as best in the world for medicine in the Times Higher Education's World University Rankings recently.

And the university's Tropical Medicine research pages note that currently recommended treatments for malaria, dengue shock syndrome, typhoid, melioidosis, TB meningitis, diphtheria, leptospirosis are all based on work conducted by Oxford scientists.

The video and the mini-website on Oxford’s partnerships in global health give a taster of some of the projects going on in over 30 different countries around the world (check the pins in the map).

It's clear even from a quick browse through these pages that the success of this research – from tackling infectious diseases like malaria, HIV/AIDS and flu to the burden of cancer, diabetes and depression is built on long-standing partnerships with local hospitals and universities.

This is not a new model. The Wellcome Trust has funded overseas units in Kenya, Thailand  and Vietnam for decades, in which Oxford faculty members based overseas work with local doctors and researchers on an equal footing. Developing training and infrastructure has also been important, helping to inspire the next generation of health leaders in the developing world.

Nor is this research happening in a bubble or an ivory tower. It is research committed to providing practical solutions that will save lives.

One example comes from last week, with an assessment of a programme in Africa to increase access to the most effective malaria drugs.

The recommended first-line treatment for malaria are artemesinin-based combination therapies, or ACTs (the effectiveness of which Oxford researchers based overseas demonstrated). But access to these drugs in many areas is incomplete, and the use of less effective, poor quality or fake drugs can make the development of drug resistance more likely – and indeed resistance has been detected in parts of South-East Asia (thanks to partnerships involving Oxford researchers based there).

Recently, the Affordable Medicines Facility for Malaria (AMFm) has sought to increase the availability and affordability of ACTs massively in a number of countries in Africa – particularly among private-sector outlets where many buy treatments when they have a fever that might be malaria.

This hasn't been without controversy (see pieces online at BBC News and The Guardian), but an independent review in The Lancet  last week suggests the data so far show the programme has transformed access to ACTs. And a smaller piece in Science, again last week, uses maps of malaria prevalence across Africa (put together by partnerships led by Oxford researchers) to argue the case for the facility to continue.

A decision will be made this month on whether to continue the AMFm in a modified form or not. As that decision comes up, a comment piece on the Lancet research, written by a group that started discussions that led later to AMFm being set up (including Oxford’s Nick White and Richard Peto), notes that where the programme was implemented to a substantial degree, AMFm met or exceeded benchmarks for availability, price, and market share of ACTs. They conclude: ‘We must acknowledge that an efficient approach to subsidising antimalarial drugs has worked, making them available in the private sector where people go to buy them.'

You get the picture. Yes, the political, economic and social aspects of delivering effective healthcare in resource-poor countries is complex. But Oxford’s overseas partnerships are delivering the evidence and change that can help save lives.