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Gut instinct

Gastroenterology research is moving towards preventative strategies

An illustrated cross section of a human torso, showing the stomachI have to declare an interest in gastroenterology because I have Barrett's oesophagus, one of the conditions being researched by our emerging leaders. But even if I didn't, I would still be excited by the developments taking place in this therapy area. It is a discipline with a small number of academics, but they are making important advances on so many fronts. 

Like just about every other area of medicine, the benefits of the genome project and our greater understanding of molecular biology are opening up new areas of research. Genetic markers associated with risk for ulcerative colitis have been identified, for example. This brings researchers closer to understanding the biological pathways involved in the disease and should lead to the development of new treatments that specifically target them.

One of the researchers profiled, Rebecca Fitzgerald, is studying molecular abnormalities in a precancerous condition. Cancers of the oesophagus, stomach and pancreas have a poor prognosis because they tend to be diagnosed at an advanced stage. However, many of these cancers have a precursor, or pre-invasive, lesion and survival could be dramatically improved with early intervention. Dr Fitzgerald is looking at biomarkers as a screening test for stratifying patients according to their risks of developing cancer. 

Allied with this potential for early intervention have been the advances in non-invasive surgery for cancer. Over the past 20 years, endoscopy has evolved from a mainly diagnostic tool to one of the most rapidly growing fields of therapeutic surgery. Lots of techniques and technologies have been developed to treat a wide spectrum of gastrointestinal diseases. For example, the overall survival rate in patients with adenocarcinoma treated by endoscopy appears to be the same as that of patients treated by conventional surgery.

Perhaps the hottest topic in gastroenterology at the moment is the interaction between the gut and bacterial flora. One of those profiled here, Mike Burkitt, is researching why gastric cancer is more likely to develop in some people infected with H. pylori. Clostridium difficile has also been implicated in a gastroenterological condition, inflammatory bowel disease (IBD). Studies have shown that IBD patients with concomitant C. difficile infection experience increased morbidity and mortality.

Increasing evidence suggests, however, that the most important factor, rather than simply an infestation by a particular pathogen, might be alterations in the balance of the different bacteria in the gut. This has been found to be common in IBD, particularly Crohn's disease, which has prompted interest in therapeutic manipulation of the flora. The third rising star, James Lindsay, is researching the therapeutic potential of probiotics. Probiotics are live microbial food supplements, which are claimed to confer a health benefit beyond inherent basic nutrition, but there have been few good studies to support these claims. However, evidence is now appearing that they have the potential to open up new therapeutic strategies for inflammatory disorders of the gut.

The Author
Neil Kendle is managing director of Kendle Healthcare

 


Dr Rebecca Fitzgerald, principal investigator, MRC Cancer Cell Unit, Cambridge

Dr Rebecca Fitzgerald describes herself as being "torn between gastroenterology and oncology". After graduating, she spent three years working at Addenbrooke's Hospital. For some of the time she was attached to the gastro department and found two of the consultants there, Graham Neale and John Hunter, particularly inspiring. When her husband got a job at Stanford University, she took the opportunity to do research in the US with George Triadafilopoulos, an oesophageal cancer specialist at Stanford, combining her twin interests.

This is an exciting time to be in medical research, as technologies have changed massively in the last 10 years, partly as a result of the genome project. She says the trick is to make sure you're still asking good questions. She and her team are using techniques such as molecular profiling to develop a new system for predicting which patients with Barrett's oesophagus, a pre-cancerous condition, are at the greatest risk of developing oesophageal adenocarcinoma, to enable treatment at a curable stage. The research is leading to the development of a non-invasive screening procedure. 

"If you want to have a career in academic medicine, you have to invest time in research as well as clinical practice," she says. "You need to be immersed in it." Funding for research is very competitive, so you have to publish in key journals and raise awareness of your work through speaking at national and international conferences. Publishing takes a lot of time, but it is essential if research is to be widely used for patient benefit.

Rebecca is increasingly involved with the pharma industry and has been impressed with the way the relationship works, especially with companies interested in the academic side. And, of course, companies have the resources for the high throughput assays that are not available to even her well-equipped laboratory. "If you want to make research progress into drugs, you have to work with pharma," she says.

Juggling everything – research, work in the clinic, teaching, plus bringing up four young sons – can be a struggle, but Rebecca believes she has a great career, which offers a combination of clinical work and research that is very inspiring. A high point of her career was when she won the Westminster Medal in 2004 for communicating her work to politicians and the public. "You have to be very determined, but I believe that if you create yourself a niche and stick at it, the world is your oyster," she says.

 

 

Dr Mike Burkitt, Wellcome Trust Research Training Fellow, Gastroenterology Research Unit, University of Liverpool

At 31 years of age, Dr Mike Burkitt is a year into his PhD and at the start of his academic career. Talking to him, you get an idea of how competitive academic medicine is and, therefore, how planned such a career has to be. Mike says that he has "one eye on the long-term all of the time" and he is already considering where things may go after his PhD. Currently he is a Wellcome Trust Research Training Fellow. One possible next step would be to take an Intermediate Wellcome Fellowship. When he applied for his current Fellowship, Mike already had a number of published papers under his belt and, importantly, on some he was first author. He had spent seven or eight years developing a worthwhile research project which, he says, is perhaps the most difficult bit.

To compete for an Intermediate Fellowship, he would need to demonstrate that he has had an outstanding start to his research career. He believes his PhD will give him good data and good publications in high impact journals. The journals that papers are published in is important. "There is an assumption that if it is in a good journal, it is probably a decent paper," he says. "More people will see it and see your name." He will also need to present at key congresses and has already started submitting abstracts for these. 

Mike studied medicine and undertook an intercalated MPhil at Liverpool, which is where he became interested in research. He chose to continue his career on Merseyside because he believes it excels in gastroenterology research and academics are well supported there. 

His research looks at the interaction between bacteria and inflammation in the gastric mucosa and, in particular, why the cancer is more likely to develop in some people infected with H. pylori than others. There is a lot of research interest in gastric cancer at the moment, with much of this being conducted by gastroenterologists rather than oncologists because of the emphasis on prevention rather than treatment.

 

 

Dr James Lindsay, clinical senior lecturer and consultant in gastroenterology, Barts and the London School of Medicine and Dentistry

Things have been changing dramatically in the world of inflammatory bowel disease. The immunological basis is better understood and there are new treatments coming along. These include biologics now and, further down the line, drugs developed as a result of better understanding of the genetic pathways that predispose to inflammation. There is also another exciting research area based on increased recognition of the importance of the interaction of intestinal flora with the intestinal immune system. One of the people at the forefront of this research is James Lindsay, whose interest focuses on manipulating gut flora with prebiotics as a therapy for Crohn's disease. 

Dr Lindsay is one of those lucky people who seems to have achieved his aims. Early in his training, he knew that he wanted to be the IBD expert at a teaching hospital and, after studying medicine at Cambridge and Oxford and basic medical training at the Hammersmith, he undertook a PhD in the immunology of Crohn's disease. He is now, he says, at the hospital he wants to be at, doing the clinics he wants to do, yet with an international involvement, which he welcomes. 

He has a growing reputation for his research, but has achieved this without compromising his clinical involvement. Ideally, he would like to spend 75-90 per cent of his time on research, but clinical work is so important to him that he devotes half of his time to that. He achieves balance by running two research teams, with full-time academics using his clinical experience and expertise, planning and grant writing experience.

He also runs one of the few clinics for adolescents with IBD. Diagnosis often occurs in adolescence, which is a time when adherence is often at its worst.

James is the endoscopy training lead at Barts and the London and on the Faculty of the European Crohn's and Colitis Organisation European workshops in Crohn's disease management.

10th November 2009

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