A desire to develop drug toxicity tests that did not involve laboratory animals encouraged a young researcher to build an artificial kidney. Made entirely of human cells, the test system can help predict whether a new drug will have harmful side effects. writes Dick Ahlstrom
Developed by Niamh Tuite, a third-year PhD student, the system involves not one but two types of kidney cell. Tuite's very clear explanation of her work to a lay audience on Tuesday captured first prize in University College Dublin's annual science-seminar competition.
Known formerly as the Merville Lay Seminars, the competition was this year renamed AccesScience, Scientific Research Unravelled. If the name has changed, the challenge hasn't. It demands that PhD students of pharmacology and biochemistry explain their research work to a large public audience without using jargon, buzzwords or technospeak.
Tuite, a pharmacology student, delivered a wholly accessible presentation entitled "An alternative approach to toxicity testing . . . Just what the doctor ordered". It described her efforts to develop a toxicity testing system based on the use of human kidney cells as an alternative to lab-animal toxicity testing.
More than 2.65 million animals were used in scientific research and testing in the UK during 2002, she points out. There is increasing pressure to reduce dependence on animal testing while maintaining safety standards in new drugs destined for human use.
Tuite received funding to develop her human-cell-test system from the Dr Hadwen Trust, a UK-based charity that supports non-animal alternatives in research, and from Ireland's Health Research Board. Her goal was to "find alternative ways to test drugs for their cytotoxicity without using animals", she told Science Today after the competition. Her answer was to use cultured human kidney cells as a way to gauge toxicity without a need for animals.
Cell cultures are already in widespread use in labs, she says. "It is a standard lab technique, but I am trying to make it more like what happens in an actual kidney. All the cells I use are actually human cells and not animal cells."
She decided to develop a system using two of the 15 or so cell types found in the kidney: epithelial cells and mesangial cells. The kidney is an elaborate filter, and epithelial cells line all of the "tubes" running through the organ. Mesangial cells do the filtering work, taking toxins out of the blood.
Cultured cells are kept alive by bathing them in a nutrient-rich broth, but Tuite found that these two cell types required different commercially produced growth mediums. She also discovered that these mediums included material derived from animal sources, something she wanted to avoid.
She decided to brew her own cell-culture medium, one that worked on both cell types. "That was one of my first and biggest challenges," Tuite says. "I wanted to get away from using animal sources and develop a formula that was more defined."
She tested 22 mixtures of sugars, proteins and growth factors, eventually coming up with one that suited both cell types. "This was the food I used in all my subsequent experiments."
She overcame the problems of a two-cell culture by inserting a filter in the growth flask. This separated the two and prevented the cultures from growing into one another. She also got away from the traditional "once a week" replacement of the culture medium in favour of a method that allowed the cells to be continually bathed in fresh medium. Her approach also allowed waste products from the cells to be taken away all of the time. "This is much more like what happens in the body. It makes it more like a human kidney," Tuite says. "What I now want to do with this system is to put in drugs and test cells and predict if the drug is likely to damage cells if given to a person."
Her initial tests involve the cytotoxicity of cyclosporine-A, an essential drug used to block the immune systems of transplant patients. The drug prevents immune-system damage to the transplanted organ but also produces undesirable side effects.
Aside from cell testing, the model kidney will help researchers pick apart the complex biochemistry associated with drug toxicity. Normal and drug-treated cells can be compared to see exactly what the cell is doing to protect itself from the drug.
She thanked Prof Michael Ryan, her supervisor and UCD's head of pharmacology, for his help in her study.
The Tánaiste, Mary Harney, presented the top prizes at the conclusion of AccesScience. She commended the efforts of its host, the Conway Institute, and its efforts towards making science accessible to everybody. It was essential for scientists to "carry their enthusiasm for science to the public" and do so "in clear terms and non-scientific language, a goal which I am happy to see echoed in the AccesScience competition".
Second prize in the competition went to Eavan Daly for her research on how white blood cells can move towards the site of infections. Brid Ryan took third prize with a presentation on survivin, a protein associated with breast cancer.
As in previous years, the seminars were hosted by Pat Kenny of RTÉ and involved a lay judging panel. This included Emma O'Kelly, education and science correspondent of RTÉ; Geraldine Kennedy, editor of The Irish Times; Michael Keating, former Tipperary All-Ireland medal winner and coach; and Ronan Wilmot, actor and director of the New Theatre.