Raising the arthritis research profile
Published on 01 July 2008
Retiring Arthritis Research UK scientific secretary Dr Madeleine Devey talks to Gillian Riley about significant advances over the past 20 years.
When Dr Madeleine Devey took up her post with Arthritis Research UK in 1990, she could only guess at the developments in arthritis research that were poised to take off in such a spectacular way. From the late 1980s onwards, the development of new techniques in biotechnology launched medical research into a new era of increasingly fast-paced discovery. Now, in 2008, about to retire, she is able to reflect on the impact of Arthritis Research UK-funded research outcomes, as well as speculate on the potential developments.
Inspired by immunology
Dr Devey’s initial fascination with immunology and autoimmune disease was fuelled by the inspiring content of some of the postgraduate immunology lectures at Birmingham University that she attended after completing her degree. Later, her interest with the subject led to a PhD at Cambridge University, where she investigated antibody responses to a variety of antigens and allergens, and in 1977 was awarded a research fellowship. She forged a successful research and teaching career at the London School of Medicine and Tropical Hygiene for nearly 13 years, then, appointed as a Wellcome Trust senior lecturer in 1979, built up her own research team across a range of basic science projects in immunology-related areas.
A challenging role
In 1990, she became the first research-qualified science secretary appointed by Arthritis Research UK. Her brief was to liaise between funding applicants and committees, provide advice to applicants, enable committees to function correctly, and develop policy, peer review process, and new funding schemes.
It was clear from the start, however, that supporting arthritis research was a challenging task. “Arthritis is not perceived as a ‘sexy’ disease, and has suffered a poor public and political profile, she says. “It’s commonly seen as a disease of the elderly that is not life-threatening, merely uncomfortable. But those involved know that it actually affects all age groups, including young people and children, with devastating effects, and it can kill.”
Dr Devey became a key driver in the development of strategies to expand the Arthritis Research UK research and funding profile. In 1990, research funding was limited to just a few award categories. Now, the charity boasts 400 active project, programme and fellowship grants in universities and institutes throughout the UK, and there are 12 specific fellowship award categories. Her enthusiasm for career development motivated the introduction of a structured approach to funding fellowships that catered for support for researchers at every level of their career. PhD, post-doctoral, career progression, research and clinical, foundation, and allied health professional fellowships were introduced to support researchers through different stages of their career.
Many of these fellowship recipients have gone on to achieve senior posts. “I’m convinced that, as a result of these fellowship schemes, we have produced some of the leaders of the future. Mark Walport, director of the Wellcome Trust, and probably one of the most influential people in medical research today, was a previous Arthritis Research UK clinical research fellow, and there exists a whole tranche of both established and up and coming scientists, Arthritis Research UK-funded in both clinical and basic research fields.
Molecular biology techniques allow researchers to identify and manipulate gene markers.
Diversity and development
One of the strengths of Arthritis Research UK, she believes, is the diversity of its funding allocation. “We fund geneticists, biochemists, physiologists, bioengineers, immunologists, and many more. They are specialists in a wide range of disciplines, including gene therapies, cell chemistry, orthopaedics, and tissue regeneration.”
A major problem with arthritis research is the range and inconsistency of disease types. It isn’t simply a case of investigating one disease mechanism and developing one ‘cure all’ drug. The cellular mechanisms involved in each disease type are highly complex and different areas of research are needed to try and establish potential therapy avenues. As Dr Devey points out: “This is a significant problem. Sometimes it takes years of research to isolate just one target molecule or mechanism and establish its influence on arthritis development. But only by doing this can we then develop therapies to bring to clinical trials and impact on patient care. Even then, within one disease type, some individuals respond to one treatment and others don’t.”
During her time with Arthritis Research UK, she has witnessed a complete transformation in research technology, particularly molecular biology. There is no doubt that processes such as proteomics and genomics have enabled rapid advances in research programmes, allowing an impressive volume of work to be completed at a phenomenal pace. Take microarray analysis - literally tens of thousands of genetic tests can now be achieved in one experiment. These techniques don’t replace bright ideas, though,’ she points out, “…they simply make the work easier to undertake.”
Important developments in research progress have used these techniques. From the 1990s onwards, molecular biology techniques allowed researchers to identify and manipulate gene markers specific to disease states, including arthritis types such as lupus and rheumatoid arthritis. Only very recently, in 2007, the discovery of two genes linked to the incidence of ankylosing spondylitis opened up new possibilities for novel therapeutic approaches. Understanding that these genes programme the cells to overproduce molecules which influence inflammation and tissue degradation, and then identifying and manipulating the molecules to block their effects, forms the basis of many potential therapeutic applications.
In terms of specific breakthroughs, Dr Devey highlights the development of anti-TNF therapy, which has transformed the lives of hundreds of thousands of arthritis sufferers and owes its development almost entirely to Arthritis Research UK funding which has supported the majority of the research process. “It is a real triumph for Arthritis Research UK,” she says. “Very few funding bodies ever solely achieve the production of a therapeutic drug from basic research concepts right through to clinical application.”
However, she points out that important developments often arise from the most unlikely sources. ‘It isn’t easy to second guess how research will progress. I remember how I felt when the early anti-TNF work was peer reviewed – it wasn’t apparent then that it was going to be so important. Now, the technology is winning awards worldwide. In the late 1980s there was even a train of thought that investment in cytokine research was a waste of money. The most important thing is to invest in good research people and Arthritis Research UK has done just that.”
Following anti-TNF therapy, B-cell depletion is probably the most significant therapy development that has reached the clinic (in the form of rituximab), she believes. “It’s another area of research that has made us completely rethink arthritis control mechanisms. However, research is incremental and doesn’t usually revolve around big developments - much of the progress has been in understanding the immunopathology of arthritis. We have seen the development of transgenic models, the identification of cytokines and other pro-inflammatory agents, the introduction of a diagnostic test for lupus, the development of novel non-steroidal anti-inflammatories (NSAIDs), the introduction of biological response modifiers, and dramatic advances in joint replacement and resurfacing technologies.
“In the future, being able to predict genetically which individuals are susceptible to specific arthritis conditions and to treat them early and appropriately would be a significant advance. Manipulating the molecular machinery that causes the autoimmune response is key: gene transfer therapies to alter faulty immune systems, the identification and blocking of target molecules causing joint damage, or the utilisation of stem cell tissue regeneration techniques would be incredible. The implications for patient care are huge. It’s a vast area of exciting research that promises significant returns, but it’s an enormous research challenge that is incredibly complex.”
Some research developments represent therapy approaches rather than the therapies themselves. “For example,” she adds, “the recognition that early and more aggressive treatment of rheumatoid arthritis can prevent joint damage – the emphasis now is on early diagnosis and rapid, combination therapy. This approach is revolutionising arthritis treatment.”
A rural retirement
When Dr Devey retires, she will still be working in a consultancy role for a few days each month for the charity. Her many retirement plans in rural Norfolk include gardening, coastal walking, fly fishing, furniture restoration, writing projects, and chicken keeping. With her husband, she plans to acquire another dog which will be company for their existing canine and two donkeys. She laughingly admonishes Arthritis Research UK for contributing to the musculoskeletal wear and tear in her back: “All that struggling around the country with heavy bundles of committee papers!”