From the top down

Have you ever thought of your stomach, bowel, colon and intestine as being like your heart? That's right, they all pump and consist in large part of muscle tissue moving food as it is processed from the top to bottom of our digestion systems. Only the period of pumping action is a somewhat different from the heart - in normal organs most of the time that is! What happens when things go wrong with gastrointestinal organs? Is there an equivalent stomach or bowel disease to a heart attack? Well, yes, there is. And for far too many patients, the consequences are just as severe including death.

Professor Bill Richards of Vanderbilt University in Nashville, Tennessee is a gastrointestinal surgeon who has been frustrated at the slow progress being made in the diagnosis of stomach and bowel disease. "These organs develop ischemias just like the heart. The only difference is that for 35 years or more cardiac surgeons have been able to get a pretty good diagnosis of ischemic heart disease and yet gastrointestinal surgeons have nothing" says Prof Richards. "For 15 years I have wanted to develop the EKG (ECG) equivalent for ischemic bowel disease. My patients arrive in my hospital with twisted bowel or ischemic bowel disease and if they get sicker we decide if we should operate." If their bowel is dead it can be removed, if their intestine is dead they die. Mortality with an ischemic bowel is around 80%. "Without an early diagnosis we can't treat with the right drugs - in some cases the heart drugs also work for us", he says in frustration.

Indeed, just like the heart, there are magnetic fields associated with the gastrointestinal tract. They are all elctromechanical pumps after all. In the case of the heart, these fields provide nice strong signals which have been used for accurate non-invasive diagnosis of heart disease for over 30 years. But on the surface of the human torso they tend to swamp out all the other fields arising from the other electromechanical pumps inside the body and in the case of the gastrointestinal tract there are several organs each producing its own characteristic field. Bill and his colleagues in the USA had been wrestling with sorting out the signals from these fields for some time without success.

Around 2002, Professor Andrew Pullan of the Bioengineering Institute at the University of Auckland got to hear about Bill Richards and his search for an ECG equivalent for the small bowel and stomach. Andrew was part of a New Zealand-based team which had developed the world's most advanced electromechanical model of the heart, and he wondered if it was possible to do the equivalent for these organs using his understanding of the modelling problems and their solution which his team had encountered. He had no idea of the extent of Bill Richard's problem let alone whether it could be solved using currently available techniques. But he had developed quite a lot about the electrical information appearing on the torso surface. He understood for example, in modelling terms, what affected the heart's electrical signals on their way to the surface of the torso. So he applied for a James Cook Fellowship which he held in 2003, plus a 12 month extension.

Part of this time was used to collect information about the organs themselves and available information on the signals they provided at the torso surface. Bill's team had no idea what to do with the data they had. Some of the problem is that the signals are so weak that superconducting "squids" were needed to detect them. Most of the time however Andrew spent working at Vanderbilt University. On the strength of his ideas, along with those of a Vanderbilt physicist, Professor Alan Bradshaw, the three received funding from the US National Institutes of Health to model the bowel and stomach so that the signals on the body surface could be understood with a view to eventually constructing an "ECG" equivalent of these organs to diagnose disease states.

Andrew, assisted by his two colleagues, developed mathematical and computer models of the human stomach, intestine and surrounding torso during the Fellowship. These models were used to simulate healthy and several diseased states in human patients. This work proved to be far more difficult than the modelling of the heart. As a result, the magnetic recordings at the body surface of patients with gastrointestinal disease were able to be interpreted. This was a great move forward for Bill Richards. Some of the work was done in animals as experimental procedures are initially carried out in animals. But abnormal gastrointestinal activity in two human patients was simulated successfully. So the Fellowship was at least as successful as Prof Pullan's dreams for it, and Bill Richards is a good bit closer to his aim for an "EKG for GI disease".

But that's not all that's resulted from the research of the Fellowship. We are all aware of pacemakers which are widely used to manage the rhythm of diseased hearts. What could pacemakers for the stomach achieve? Well, currently Andrew is working with investigators at the University of Galveston, Texas on a "gastric stimulator" which will empty the stomach and intestine more slowly. In obese patients the stomach and intestines empty too quickly so this will add to the arsenal of interventions for fighting obesity. Or vomiting could be controlled using stimulators. A small device could find a large market. Just as replacement heart valves have become pretty common, it is expected that similar replacement valves could be used at the top of the stomach and top of the intestine to reduce reflux and so on. Andrew is now working with surgeon Professor John Windsor of the University of Auckland on this opportunity.

In an even more unexpected outcome, work has begun with researcher Jules Kieser, Professor of Oral Surgery of the University of Otago Dental School who wishes to model jaw mechanics and swallowing. "Dentistry researchers have almost always focussed on immediate problems but we really need to look at the whole mouth. It's too complicated without a model. Andrew has given us a new way of looking at the mouth. And we can make big progress on understanding sleep apnoea by modelling the back of the mouth" says Prof Kieser "We need to know what happens with a big tongue, a soft palate and a fat old neck - it's a recipe for disaster for the patient!" Prof Kieser is also part of a team including Massey Univerrsity researchers and Heinz Wattie seeking new non-obesogenic foods and modelling the mouth and swallowing plays a part there too. Very little is known about the chewing and swallowing in obese patients. In education of dentists too, Prof Kieser says a virtual mouth has turned out to be far superior in training dentists. 'Without the modelling paradigm proposed by Andrew, we couldn't get going. Andrew's contribution to our work is very valuable" commented Prof Kieser. So the James Cook Fellowship has taken us the whole way from modelling the top end of the torso to the bottom.

A direct outcome of the work at Vanderbilt has been the filing of a patent and a collaboration between Auckland UniServices Limited, Vanderbilt University and a company developing the technology for detecting the magnetic fields of the torso, processing them, and interpreting them in the form of a diagnosis. A spin-out of the research is that, now, Professor Pullan has added four postdoctoral fellows and six graduate students to support all the ongoing collaborations following the success of the James Cook Fellowship research. . Overseas funds are being raised to validate more thoroughly the gastrointestinal model and to investigate cell physiology in heart and intestine at the University of Nevada in Reno. Academically, a number of publications have appeared from this work.

Currently there are no non-invasive tests for diseases of the gastrointestinal tract. But Bill Richards in June 2007 is delighted at progress. "Andrew Pullan's work on pathways has absolutely contributed to this progress. He has shown us the way forward to determining the direction, location and extent of these disorders" he says. "His work enabled us to get our research refunded recently and now with Leo (from Andrew's lab in Auckland) we are going gangbusters!" According to Richards, it has been an incredibly worthwhile collaboration with each collaborator looking at the problem from a totally different angle. It has made them, he says, the best group for gastrointestinal research in the world.

So what is the return to New Zealand? Well, it's early days for such a new medical field, but before long a lot of New Zealand patients with a relatively poor outlook can expect to benefit from one of the several outcomes of this work. Meanwhile the benefits continue to accrue for New Zealand researchers with funding from overseas and acknowledgement of their work.

Back in New Zealand, Andrew Pullan is amazed at what has been achieved by the Fellowship " The relatively non-prescriptive nature of the Fellowship enabled a freedom to explore a number of avenues, most of which have turned out to be far more fruitful and important for clinical outcomes than anybody including myself imagined. Particularly, the travel provision allowed for much more meaningful collaborations and exploitation of the research"