SOMETIMES good quality scientific research disproves rather than proves a theory. That experiments can wipe out what appears to be a perfectly good idea is not a failure, but rather a valuable piece of information that allows researchers to rethink and pursue new theories.

Graham Love, co winner of the first Merville Lay Seminar lecture series, described his mixed fortunes in validating one theory in his PhD research while trashing another. His specific area of interest was a chemical substance, endothelin, produced in various tissues of the body. He wanted to determine what role, if any, that endothelin had in controlling the "leakiness" of blood vessels. He also wanted to determine how it interacted with another group of substances, cytokines, which are involved in diseases related to hardening of blood vessels.

Endothelin, a small protein molecule known as a peptide, was discovered by a Japanese research team in 1988, explains Love. It was found to be one of the most powerful blood vessel constrictors yet discovered, and so became an immediate target in understanding blood pressure control.

If blood vessels constrict - reducing blood flow - blood pressure increases. It falls if blood vessels are made to "relax" or open up.

Well established tissue culture techniques were central to Graham's research. This involves taking a particular type of cell and growing it on in the laboratory. Special tissue culture flasks were used to hold the cells, which were bathed in nutrient mixtures which sustained the tissues outside the body.

The design of the test assemblies and the experimental procedures were his own as sole researcher on this project. He depended on further assistance from his supervisor, Dr Alan Keenan.

The leakiness of blood vessels is a factor both in health and disease, explains Love. "Blood vessels in an area of injury become leaky to allow immune system cells into the tissues where damage has occurred." The body first recognises damage then releases a chemical response to both protect against infection but also to aid healing.

Love created an experiment using endothelial cells, which can produce endothelin, to examine whether endothelin helped promote leakiness. These cells occur as a thin layer which lines the inside of blood vessels, an ideal location if they were to contribute to changes in the blood vessels.

Cultured endothelial cells "actually retain many of the characteristics of the cells in the body", he explained, so the test rig results would have some validity when examining cell leakiness in the presence of endothelin.

The rig, he said, was like a bottomless half pint glass resting inside a pint glass. A layer of cells were cultured to provide a thin barrier at the bottom of the half pint glass, with a liquid medium existing in both glasses to sustain the cells.

Endothelin was added to the smaller container and a blue dye was added. If the theory was correct, the cells would become leaky in the presence of endothelin, allowing the dye to seep across the barrier.

Amounts of endothelin added were varied, as was the time allowed for the dye to move across. Love found, however, that endothelin did not seem to be a factor in changing leakiness, so this theory was disproved.

A different test rig was used to study the second theory, that endothelin interacted with cytokines in a way that might contribute to the risk of stroke and blood clots.

Cytokines are known "to play a role in every process in the body," Love explains, but this can be for good or ill. They are known to be involved in the process that causes the build up of fatty plaques in blood vessels. These plaques block up the vessels like mineral deposits in old water pipes.

Reduced blood flow greatly increases the risk of a complete blockage from clotting. If endothelin levels increased in the presence of cytokines, then this presumably heightens the risk because of the peptide's ability to constrict vessels still further.

Graham used a rig which had a layer of endothelial cells surrounded by nourishing solution. After establishing the "normal" output of entothelin, cytokines were added to see if output changed. The answer was an emphatic yes. "What we found was a significantly increased endothelin production from the cells," with increases dependent on the type of cytokine added to the solution.

Graham's research raises further questions in our understanding of how circulatory diseases progress. We know that there is more endothelin about when cytokines are present, but does this directly contribute to disease progression. If so new drug therapies could be developed that counteract the endothelin, but these developments require much further research by others building on Graham's work.

Graham will complete his PhD in October, but he has shocked many of his colleagues and friends after deciding to leave research and become a business consultant. "It is a complete break. A lot of people had their eyebrows raised," he says.

"I actually wanted to get into business. I wanted more interaction with people," he says. He was unhappy with the lack of a career structure for researchers here. Limits to income were also a problem, he admitted. The company hiring him suggested that his technical training was central to its decision to go for a technical person. "The problem solving and analytical capabilities were seen as desirable," Graham says.