Features

Michelle Lee first set foot in Gabon in 2001: 'I went with just a backpack expecting to stay three weeks, but ended up being the project manager there for six years,' she tells me.

Now a DPhil student at Oxford University's WildCRU, working on land-use and conservation planning, back then Michelle gave up her desk job at the Smithsonian Institute in Washington to fly out and take over after the manager of the Institute’s Gabon biodiversity project quit.

Gabon is a haven for wildlife and a hotspot of global biodiversity. Its small and highly urbanised population, along with its substantial petroleum and mineral deposits, have reduced typical pressures on land conversion. Consequently, Gabon boasts some of the largest remaining tracts of pristine tropical forest in the world.

During her time spearheading the Smithsonian project, Michelle became acutely aware not only of Gabon's significance for conservation but also of the sparse ecology and land-use data that was crippling conservation efforts. 'When I started my doctoral studies there wasn't even a national bird or mammal list compiled, let alone any species-distribution maps,' she recalls. 'There were also no maps of existing land uses, and the latest habitat maps were from the 1970s.'

Over the past four years, Michelle has worked with local experts to gather this vital data. In a process similar to that used by the IUCN's for their Red List threat assessments, she has completed a prioritization analysis of Gabon's terrestrial vertebrates and produced distribution maps for the top priority species. She has also updated the nationwide habitat maps for the country and assessed how different habitat types are allocated across different land uses throughout Gabon.

Her research is providing a foundation for science-based land use planning and policy development in Gabon, whose government is unusual amongst its neighbours in its strong commitment to fostering biodiversity preservation and ecotourism, alongside economic expansion.

'The slow and painstaking task of prioritisation and mapping allowed me to identify key habitats that were poorly represented in Gabon's national reserve system and to propose improvements to the current protected area network,' she tells me.

Michelle has presented her scientific findings directly to the head of National Parks, and is working with the government to identify areas that require more field verification. 'As a signatory to the International Convention on Biological Diversity, Gabon is legally required to meet certain targets for habitat and wildlife protection,' she explains. 'My research enabled the government to see where they fell short of these targets, and together we are planning scenarios to address these shortfalls and improve the efficacy of the reserve design.'

A large part of Michelle's success at conveying her research findings and expert opinion to Gabon's policy-makers comes from the fact that she drew together the many disparate sources of data needed for the planning process.

'I think that being in-country helped me figure out what would be helpful for us to know, and then I tried to address this.' However, as she is quick to point out, the process of being heard required more than just researching the right questions and a government willing to listen. 'My involvement would probably have been impossible without my history of working in the country and my understanding of the context on the ground,' she says. 'This has helped me gain the confidence of the people involved. So I am able to present conservation options that I think might be both internationally appreciated and politically palatable.'

What she only casually alludes to though, is the importance of persistence, perseverance, and passion. 'For a long time I carried around these big maps of mineral depositions and habitat and wildlife distributions wherever I went,'she remembers, smiling. 'I would unroll them at any opportunity and encourage people to see how conservation and development could be accommodated and planned for together in a spatially-structured scientific process. I guess I eventually got my message through. Or perhaps they just got sick of seeing me carrying them around!'

When I ask Michelle for her advice to other conservation scientists, she replies that patience, flexibility and the ability to compromise are critical for negotiating the path from science to policy.

'Trying to do conservation science in a developing nation, even one as environmentally aware as Gabon is a balancing act. I realised early on that I could not adopt a 'conservation agenda' if I wanted to achieve the greatest outcomes for environmental sustainability,' Michelle says. 'Gabon is trying hard to balance job creation, food security, and economic development alongside biodiversity retention and carbon sequestration. At some point, detrimental impacts are unavoidable and you have to make difficult decisions. Conserving 50% of elephant habitat is great, but it also means that you are prepared to lose 50% of their habitat.'

This means that transcending the divide between research and policy requires a slightly different breed of scientist. One who is willing to adapt their focus and adjust their expectations of outcomes, one who can balance the analytically correct answer with what makes real-life sense, and one who views science as a means of solving a problem rather than an end in itself.

As Michelle notes: 'Applied science is an entirely different process to research science, as it should be. Because of my background, I am able to wear both hats, and operate as research scientist in my doctoral studies and as applied scientist when I interact with the Gabonese government. Ultimately, though, we need both.' 

Shelly Lachish is a Research Fellow in Oxford's Department of Zoology and a freelance writer.

Fruit flies may have more individuality and personality than we imagine.

And it might all be down to a bit of genetic shuffling in nerve cells that makes every fly brain unique, suggest Oxford University scientists.

Their new study has found that small genetic elements called 'transposons' are active in neurons in the fly brain. Transposons are also known as 'jumping genes', as these short scraps of DNA have the ability to move, cutting themselves out from one position in the genome and inserting themselves somewhere else.

The inherent randomness of the process is likely to make every fly brain unique, potentially providing behavioural individuality – or 'fly personality'. So says Professor Scott Waddell, who led the work at the University of Oxford Centre for Neural Circuits and Behaviour: 'We have known for some time that individual animals that are supposed to be genetically identical behave differently.

'The extensive variation between fly brains that this mechanism could generate might demystify why some behave while others misbehave,' he suggests.

The Oxford researchers, along with US colleagues at the University of Massachusetts Medical School and Howard Hughes Medical Institute, were able to deep-sequence the DNA from small numbers of nerve cells in the brains of Drosophila fruit flies.

They identified many transposons that were inserted in a number of important memory-related genes. Whether this is detrimental or advantageous to the fly remains an open question, the researchers say.

Scott Waddell notes that neural transposition has been described in rodent and human brains, and transposons have historically been considered to be problematic parasites. New insertions of transposons can on occasion disrupt genes (as was found in this study), and transposons have been associated to some human disorders such as schizophrenia.

However, it is also possible that organisms have harnessed transposition to generate variation within cells, and by extension create variation between individual animals that may turn out to be favourable.

Scott Waddell wants next to determine whether neural transposition provides an explanation for variation in fruit fly behaviour by finding ways of halting the process in flies in his lab.

The peat swamps of Sabangau are home to vast array of wildlife including the world's largest orangutan population.

For the last three years OxSciBlog has been following work by Dr Susan Cheyne of Oxford University's WildCRU, one of the leaders of the OuTrop Project, to study and protect the creatures and habitat found in this corner of Borneo.

Now you can take part in a free public vote to help save the home of all Sabangau's special primates, rare clouded leopards, bears, and other wildlife. Simply go to the National Geographic Germany website where you can vote for OuTrop (see 'Protect and Restore Orangutan Habitat, Southern Borneo') to receive funding from the European Outdoor Conservation Agency (EOCA).

If successful EOCA funding will go towards restoring orangutan populations in the peat swamp, analysing the needs of the forest apes, and making sure any solution is sustainable and also benefits local people working there.

How would you look for something that can be in two 'places' at once?

The answer, according to Oxford University research into a quantum phenomenon called superposition, seems to be to ask where it isn't rather than where it is.

'Superposition allows an atom to be simultaneously 'here' and 'there'. Electrons behave like tiny magnets which can point both North and South at the same time,' explains Professor Andrew Briggs of Oxford University's Department of Materials. 'This is a distinctive quantum effect; it is quite different from anything in our intuitive every day experience of the world.'

Professor Briggs tells me that you can imagine an electron as being rather like a spinning top, as it spins it generates a magnetic effect.

'Just as a magnetic compass aligns itself with the Earth's magnetic field, because its energy is lower when it points that way, so a single electron in a magnetic field has a different energy depending on which way its spin points,' he says. 

But in the quantum world nothing is easy: try to look directly at which way this 'quantum compass' is pointing and the very superposition you wanted to catch in the act - of it pointing north and south at the same time - is destroyed. Instead the superposition state will be replaced with one where the magnet is pointing either north or south at random.

To get around this problem Dr Richard George and others from Oxford worked with colleagues at TU Delft in the Netherlands to prepare a series of experiments.

The researchers used the magnetism of a single atom of nitrogen trapped in a high-purity diamond as their 'quantum mechanical compass'. Under laser light, the nitrogen atom fluoresced according to how it was magnetised.

Rather than asking, 'Is the magnet pointing north or south?' the team asked, 'Is it pointing not east?' Measurements that confirm 'not east' were still compatible with the quantum superposition of pointing both north and south at the same time. The researchers studied three successive rounds of measurement on the nitrogen quantum compass, and used correlations between different rounds to prove the presence of quantum superposition in their system. 

The team recently reported the results in the journal PNAS.

'We had previously performed experiments in which the nuclei of our atoms had two states available to them. Now we have extended this to a superposition of three states, if you like North, South, and East,' Professor Briggs explains.

'The investigation involved an intermediate measurement, which was equivalent to opening one of three boxes and seeing if a ball was not in it. We showed that not only could you not tell which box had been opened; you could not even tell whether a box had been opened. This in turn, thorough some rather detailed reasoning, allowed us to prove experimentally some fundamental conjectures about the nature of reality.'

According to Professor Briggs this work is pushing the boundaries of 'quantumness' and developing techniques that will help to investigate whether quantum superposition applies to larger and more complex objects.

Dr George adds: 'Our confirmation of these subtle quantum predictions is an important step on the road to transplanting quantum mechanics from a theoretical and laboratory curiosity and into the devices which we use in commerce and everyday life. Our vision is to scale up and build computers in which every 'bit' is replaced with a 'quantum bit' that uses superposition as an integral part of their operation.'

All human clinical trials of new treatments begin with phase I, where drugs are tested in isolation to confirm their safety. Yet most effective cancer treatments use a combination of drugs, so-called 'multi-agent' treatments. After phase I trials are completed, it can sometimes take up to two years before multi-agent trials are approved, never mind conducting the lengthy phase II and III trials necessary before a new drug finally reaches the market.  

Professor Adrian Harris at the University of Oxford is currently leading a new type of trial which aims to significantly accelerate multi-agent drug development. Working with the Cancer Research UK Drug Development Office (DDO) and AstraZeneca, Professor Harris' team are now running phase I trials of a new cancer drug, AZD0424.

The big difference with this trial is that researchers and patients will not need to spend years waiting for approval after phase I is complete. Since the trial was awarded flexible approval right from the start, researchers will be able to move straight to multi-agent trials to begin testing the new drug in three different 'arms'. Each treatment arm will pair AZD0424 with a pre-approved cancer drug from a shortlist of 5.

All drugs on the shortlist have been approved for use in the trial, and the final three partner drugs will be chosen based on experiments in mice currently being undertaken at the Edinburgh and Belfast Cancer Research UK Centres. Refining the choice of partner drugs while phase I trials are underway in Oxford adds a further time saving to the development process, and is possible thanks to the advanced approval process.

'Although the drug may be effective on its own, we expect substantial synergy in combinations,' says Professor Harris. 'So the strength of this trial is that we are able to pair it with other drugs without having to wait for further approval between stages.'

AZD0424 works by partially blocking two proteins, Src and ABL1, which are abundant in cancerous tissue. These proteins are important for cell growth, metastasis (the spread of cancer) and blood vessel development, so blocking them helps to halt the growth of cancer cells and shuts off their blood supply. Researchers have selected a list of drugs whose effects are expected to complement AZD0424, and the results from Edinburgh and Belfast will help decide which ones to use.

'By pairing this drug with others, we can block multiple signalling pathways to improve the overall treatment,' explains Professor Harris. 'We hope that they will have additive or synergistic effects which could reduce or inhibit tumour growth.'

When the overall effect of multiple drugs is equal to adding up their individual effects, this is known as additive. Synergistic effects are when drugs interact such that the result isgreater than the sum of their individual effects. The partner drugs have already been shown to work individually, but this trial is about finding their combined effects in humans.      

'With conventional trial structures, it's unlikely that we would be investigating this drug in a multi-agent trial,' says Professor Harris. 'The flexibility to adapt the treatments used in the multi-agent stage will allow us to match specific patient groups and cancer types to the most promising drug pairs for their circumstances. By removing the considerable cost and delay of waiting for approval between stages, we can widen the pool of viable treatments and accelerate drug development.'

Yet doesn't removing this stage compromise the safety of the trials? Not according to Professor Harris. 'The approval granted before phase I was no less rigorous than it would have been if it was given between phases,' he explains. 'All of the drugs used in the trial have been tested for safety. One of the reasons for choosing AZD0424is that similar drugs have minimal side effects, so it's a relatively low-risk compound to begin with. We will also reduce the dosage when we begin the multi-agent phase.'

Of course, this multi-arm trial design isn't suitable for all drugs. It does take a little longer to get advanced approval in the first place, delaying the start of phase I. The design is well suited to a drug like AZD0424, which is expected to be most effective when used with other drugs. It is also important that patients in the trial receive good clinical care at all times.

'Professor Mark Middleton leads the clinical side,' says Professor Harris. 'He's currently running the phase I clinic, and every day he provides the highest quality of care to all patients in the trial. It's important that patients are treated holistically in the clinic.'

If the trial proves successful, Professor Harris hopes that the drug could be licensed for use with partner drugs within 4-5 years. 'It's worth remembering that by using combined approaches, including radiotherapy and surgery, half of common cancers are now curable,' he adds. 'A lot of people don't realise how far we've come in recent years. While there is still much work to be done, existing treatments for many cancers are highly effective. People often forget that, and it's important to focus on the positive sometimes.'

The AZD0424 trial is supported by the Cancer Research UK Drug Development Office and AstraZeneca