Features

After his trip to Guyana last year Oxford's George McGavin recently led an expedition to Papua New Guinea as part of BBC One's Lost Land of the Volcano.

The first part of the series went out on Tuesday [watch it on BBC iPlayer] but, with two more episodes still to come, I quizzed George about his latest adventure, the new species the team discovered and how they coped with humidity, leeches and lava bombs:

OxSciBlog: Why is Mount Bosavi such an interesting place to study?
George McGavin: Mount Bosavi, which rises to a height of 2,507 metres (8,225 ft) above sea level, is the collapsed cone of an extinct volcano in the Southern Highlands of Papua New Guinea that last erupted some 250,000 years ago in the Pleistocene.

What makes this area so interesting is that it is remote, relatively unexplored and the difficulty of accessing the crater means that hunting pressure on the animals inside is currently very low. Additionally, the top of Mount Bosavi, being an isolated montane habitat, will harbour species not found in the surrounding lowland forest.

OSB: What species there captured your imagination?
GMcG: The forest is filled with weird and wonderful species from pygmy parrots and giant rats to squeaking beetles and grunting fish. Halfway through the expedition I found and photographed a small group of caterpillars, which I had never seen before. They sat on a branch in a snake-like group and when threatened thrashed around violently.

The only way of finding out what they were was to rear them through to adulthood in a cage. They pupated but nothing happened until the very last morning when we were due to leave. I had transferred them into a small box in the hope that they might emerge - and they did! - I opened the box to see three large and colourful, fruit-piercing noctuid moths (Eudocima iridescens).

OSB: What were the challenges of filming in the crater?
GMcG: Filming in rain forest is tough on equipment and people. Constant high humidity does not go well with sophisticated microelectronics and all the essential camera gear was kept in custom built hotboxes over night to make sure they were dry - even if we were not.

One team filmed inside the 'white water cave' of Mageni on New Britain and had to wade, scramble and climb their way deep into the heart of a mountain. It was like travelling through the world's greatest jet-wash. The enormous quantities of water and spray gave the cameras and sound equipment a hard time but they still managed to film some extremely exciting new passages as well as the cave’s natural inhabitants, bats, leeches and cave crickets.

Another smaller team visited Tavurvur an active stratovolcano near Rabaul in East New Britain. During the time we were filming, Tavurvur became unusually and spectacularly active, throwing up huge plumes of ash and ejecting some large volcanic ‘bombs’ a kilometre into the air some of them flew over and landed near our camp site - forcing a very hasty early morning retreat.

OSB: Why is protecting the wildlife of places such as Papua New Guinea so important?
GMcG: Recent analyses of thirty years of satellite imagery for Papua New Guinea have found that 19.8 million acres of forest was lost between 1972 and 2002. At the rate forest is being cleared or degraded more than 80 percent of the country's accessible forest - and more than half of the total forested area will be gone or severely damaged by 2021.

The loss of what is the world's third-largest rain forest would see the extinction of a unique flora and fauna and have devastating and far-reaching effects on the physical environment, regional weather patterns and the lives of the people that live there.

And it’s not just the forest and its species we will lose. As the process of logging releases huge amount of carbon dioxide into the atmosphere, continuing deforestation make it virtually certain that the world as a whole will not be able to escape the worst effects of global climate change.

The next part of Lost Land of the Volcano will be broadcast on BBC One, 15 September at 9pm, with the third part airing on 22 September at 9pm.

Dr George McGavin is an Honorary Research Associate at the Oxford University Museum of Natural History.

Currently everyone is interested in China – whether its China’s astonishingly rapid emergence as an economic powerhouse, its place as a huge producer and consumer in a globalised world, its role in global politics, its part in climate change negotiations, or as a stage for a fabulous Olympics.

China is also fascinating from a medical and public health point of view. It goes without saying that China has a vast population of over 1.3 billion. But that population is spread between cold northern latitudes and tropical beach resorts in Hainan, and lives both in underdeveloped rural areas and the crowded international cities of Shanghai and Hong Kong.

It’s also an ageing population, as the effects of the rapid improvement in the general health of its population and birth control policies play out.

Changing lifestyles
On top of all that, rapid economic change has led to equally fast changes in many people’s incomes, diets and lifestyles. As a result, disease patterns have altered remarkably over the past 40–50 years so that chronic diseases such as heart attacks, diabetes and cancer are now the biggest killers rather than infectious diseases and diseases of poverty.

Coupled with relatively well established nationwide healthcare infrastructure, this means China is a very good place to carry out large-scale medical research. Clinical trials of new treatments carried out here, as well as observational studies that can reveal risk factors for chronic diseases like heart attacks and cancer, will be useful not only for public health policy in China but also to inform healthcare in both the developing and developed world.

‘There’s much that we can try to understand. In China there’s a huge unexplained variation geographically in many chronic diseases,’ says Professor Zhengming Chen, director of the China Program at the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford.

‘For example, twenty per cent of adults in rural Sichuan would die in middle age from chronic lung disease back in the 1990s, but deaths from this disease were more than 10-fold lower in many other rural areas. Smoking only accounts for part of this huge variation. Similarly, stomach and oesophageal cancers vary greatly in different regions. There is also a four-or-five fold difference in stroke death rates between different parts of China, with rates in China on average being more than five times as high as in the UK. We’d really like to understand the factors that lead to these differences to inform preventive and therapeutic measures.’

Our news pages announce today that CTSU has just extended and renewed a partnership with Fuwai Hospital of the Chinese Academy of Medical Sciences through the China Oxford Centre for International Health Research. This will further strengthen CTSU’s 20-year long collaboration with medical scientists in China and will provide researchers with dedicated new facilities in China for the next 20 years.

Where it all began
CTSU’s collaborative research with medical scientists at the Chinese Academy of Medical Sciences and the China National Centre for Disease Control started during the early 1980s, initiated by Professor Sir Richard Peto and Professor Rory Collins, co-directors of CTSU.

It began with a landmark study that mapped the regional variation of incidence of chronic diseases, and possible lifestyle and blood determinants of disease rates, at a population level across 69 rural Chinese counties. It grew to include large-scale randomised trials that have resulted in changes to clinical practice worldwide for heart attacks and strokes, and now involves one of the world’s biggest ever blood-based epidemiological studies of the determinants of chronic diseases, involving studying and monitoring the health of over 500,000 people for up to 20 years.

‘We have had the privilege of collaborating with many distinguished medical scientists in China since the early 1980s, probably well before anyone started talking seriously about China,’ says Zhengming Chen. ‘It was not an easy start, and took quite a while to convince many funding agencies and pharma what collaboration with China can really offer.’

That’s changed greatly now that CTSU has demonstrated again and again that you can get collaborative research projects carried out cost effectively in China, with rapid recruitment and high-quality data. These projects have provided clear evidence that can improve clinical practice and save lives. In doing all of this, CTSU has also built up a phenomenal set of partnerships with Chinese research institutions and a network of hospitals across the nation.

One of the early studies that began to change people’s minds was CAST, the Chinese Acute Stroke Trial. Carried out by CTSU and Fuwai Hospital, this looked at whether aspirin as an antiplatelet agent was beneficial if taken soon after the most common type of stroke. Over 20,000 patients from more than 500 Chinese hospitals were randomised to receive either aspirin or a placebo within the first 48 hours of a suspected stroke, at the same time as a similar study was being carried out in the West coordinated by Edinburgh University. This showed definitively that trials could be carried out in China to the same standard as in the West.

‘Even 15 years ago when this was carried out, the number of stroke patients receiving a CT scan in Chinese hospitals was actually higher than in the international study in the West,’ notes Zhengming Chen. The data from both studies were analysed together and showed a clear net benefit for aspirin after a stroke, with the results being published in The Lancet.

More recently, the Second Chinese Cardiac Study (COMMIT-CCS2) involved 46,000 patients from 1250 hospitals in China in investigating the effects of two different emergency treatments for heart attacks. The results, published in 2005 in The Lancet, gave clear evidence for the first time that adding clopidogrel, a new antiplatelet agent, to aspirin can further reduce the risk of mortality for patients after a severe heart attack. The drug is now used in the back of ambulances in many parts of the world.

Biobank reaps dividends
Of all the projects in China involving CTSU, the most impressive so far – in terms of the size, scope and potential scientific significance – is the Kadoorie Biobank Study led by Professor Zhengming Chen at CTSU and Professor Liming Lee in Beijing.

This joint project between CTSU and the China National Centre for Disease Control has $10 million in funding from the Kadoorie Charitable Foundation in Hong Kong, as well as core funding to CTSU from the UK Medical Research Council. It has recruited over 500,000 volunteers over 35 years old from 10 different urban and rural areas across China, and the health of study participants will be closely monitored over the next few decades.

The project started in June 2004 and finished recruiting all half a million volunteers by July 2008. Each of the participants filled out a comprehensive questionnaire on a laptop covering their lifestyle, diet and medical history, completed a range of physical examinations, and provided a blood sample for long-term storage.

This staggering amount of data and the availability of blood samples for later analysis will be an enormously powerful and rich resource in investigating the environmental and genetic causes of many common chronic diseases among Chinese adults over the coming decades. The long-term follow up for deaths and hospital admissions among the 500,000 volunteers has just began, helped by a recent grant of £2.5 million from the Wellcome Trust.

CTSU’s work has shown that high-quality, large-scale medical studies can be carried out in China efficiently, swiftly and economically, providing clear evidence about the efficacy of treatments and revealing risk factors for common diseases. The collaborative centre announced today at Fuwai Hospital will cement this work for the future and add to CTSU’s capabilities in China.

The sequencing of more and more genomes is showing not only how we differ from other animals but also how much we differ amongst ourselves, while large-scale efforts to scan the length of our DNA has pinpointed hundreds of genes linked to common diseases.

To understand more about some of the implications, OxSciBlog caught up with Julian Knight of the Wellcome Trust Centre for Human Genetics, who has just had a book published by OUP titled Human Genetic Diversity.

OxSciBlog: The Human Genome Project revealed one DNA sequence for all of humankind back in 2000. What’s happened since?
Julian Knight: The Human Genome Project was a remarkable scientific advance which has revolutionised genetics and biology. Armed with this route map or ‘blueprint’ of the human genome, scientists have since been able to study specific genes in the genome, understand how expression of genes is regulated and perhaps most importantly discover how we differ as individuals in our genetic makeup.

OSB: How do individuals vary genetically? Are we very diverse as a species?
JK: Although as a species we all share the great majority of our genetic sequence, there are important differences between individuals. This affects not only our physical appearance, but also how our normal physiology operates and our individual susceptibility to disease.

As technology has advanced, we have found that genetic diversity occurs more commonly than expected. This ranges from microscopically visible differences in chromosome number and structure, to very fine scale variation at the level of single DNA base differences – often described as ‘single nucleotide polymorphisms’ or ‘SNPs'.

There have been major efforts to understand this genetic diversity through collaborative studies such as the International HapMap Project and recently the 1000 Genomes Project which will give us a much more complete understanding of common and rare variants.

OSB: What do we know about genetic variations in different people and their susceptibility to disease?
JK: Genetic variation between people allows us to look for association with disease susceptibility. For some genetic variants, their effect is highly significant and typically they are rare in a population, leading to classical ‘genetic’ diseases showing Mendelian inheritance in families such as cystic fibrosis or Huntington’s disease. Linkage analysis has successfully identified the genetic basis of many such diseases.

More recently, the genetic contribution to common diseases such as type 1 diabetes or asthma have been established, based on genome-wide association studies using hundreds of thousands of SNP markers.

OSB: What has that taught us about the causes of disease and can we expect major advances in treatment as a result?
JK: The recent explosion in knowledge about the genetic basis of common diseases made possible by the genome-wide association study approach has provided important new insights into the basis of disease, as well as potential new drug targets. There are also remarkable opportunities for ‘personalised medicine’ in which therapies can be tailored to the individual patient to maximise benefit and minimise risk of adverse effects.

However our understanding of the genetic basis of susceptibility to diseases such as diabetes remains incomplete as to date we are only explaining a minority of the genetic risk.

OSB: Can we expect a time when it is routine to scan each of our genomes so we can receive drugs and treatment to fit our personal genetic profile?
JK: Personalised medicine based on genetic testing will become a routine part of healthcare but much work remains to be done to more fully understand the science, and to address the many social and ethical issues which arise. Already genetic testing is helping in the safe use of particular drugs, such as for treatment of HIV infection or use of the anticoagulant drug warfarin.

OSB: By tracing back genetic variation in humans, is it possible to learn more about our origins?
JK: The study of different types of genetic variation has been very informative in understanding our ancestral origins, both over recent generations but also in evolutionary timescales. For example, this has provided important supporting evidence for the proposed origins of anatomically modern humans in Africa, as well as particular selective pressures operating in human populations in the recent past, such as malarial infection.

OSB: And can we answer the question of whether humans are still evolving? Is there any evidence of selective pressures on the genetic variations we see?
JK: Genetic variation continues to arise and provides a substrate for ongoing evolution. Differences in the frequency of particular genetic variants and the combinations in which they occur can leave so-called ‘signatures of selection’ in particular regions of the human genome reflecting past selective pressures. This is well illustrated by lactase persistence, a trait which is found in different human populations related to dairy farming. Specific genetic variants involving the LCT gene are found to confer lactase persistence, for example in European populations.

Puffins, with their bright beaks, upright walk and all-action lifestyle, are amongst the most familiar and beloved of Britain's coastal birds. But they are also mysterious, as Oxford scientists explain in The One Show tonight.

Tim Guilford of Oxford University's Department of Zoology studies Atlantic Puffins [Fratercula arctica] on Skomer Island, Pembrokeshire: 'People literally flock to see these beautiful birds busy with their comings and goings to their cliff-top burrow nests during the high summer,' Tim tells us.

'By August, though, the Puffins have gone for the winter. The question is: where?' 

He explains that, like many seabirds that leave our shores every summer, their over-wintering behaviour remains little understood. 

'Traditional methods for studying seabird movements involve the recovery of uniquely numbered metal leg rings from birds found washed up on beaches or found in fishing nets,' he says.

'Logging the distribution of such ‘ringing recoveries’ can provide an idea of where birds go on migration. But Puffin recoveries are few and far between, providing poor resolution and suggesting that they may overwinter far out at sea.'

But this seasonal 'blank' is now being filled in thanks to the development of miniature tracking technologies. Biologists at the Department of Zoology in Oxford, and Microsoft Research in Cambridge, have been using archival light logging devices built by the British Antarctic Survey to record daily positions of Puffins breeding at Skomer Island throughout the winter. 

These 'geolocators' weigh just 1.5g and can be carried safely on a leg ring, and use stored light level records to provide an estimate of Latitude (day length) and Longitude (time of midday). The accuracy is not high compared to satellite tracking (around 100-200km), but still offers a remarkable view of the migratory behaviour of birds weighing just a few hundred grams. 

Tim adds: 'The aim of the project is to understand the at-sea behaviour and movement ecology of a range of predatory seabirds, including the Puffin.  Similar studies on different colonies are ongoing at other institutions, such as CEH Edinburgh.'

'It will be particularly interesting to determine whether there are differences in over-wintering behaviour between Puffins breeding on the Pembrokeshire islands, where breeding and over-wintering survival have been relatively high in recent years, and those breeding in the North East of the UK where birds are sometimes much less successful.'

The project is still in its early stages, as the researchers gather data on the Puffin's mysterious winter behaviour, but we hope to update you with what they discover.

An item on this research airs on BBC One's The One Show on 1 September 2009 at 7pm.

UPDATE: If you missed last night's programme you can watch the report on BBC iPlayer [23:33]

Whilst it officially opens tomorrow, if you're in Oxford you can already enjoy the new From Earth to the Universe exhibition in University Parks today.

The exhibition deserves a special mention, not least because one of the 28 panels is sponsored by our friends at Galaxy Zoo, the project that gets members of the public involved in online astronomy research.

The project is just part of festivities for the International Year of Astronomy.

Images: Thanks to Lorna Stevenson for these photos.