Leading Irish scientist Stephen Sullivan has followed his passion for stem-cell research all the way to Harvard. He tells Dick Ahlstromabout his work there.
Two scientific discoveries changed Dr Stephen Sullivan's life. Together they launched him on a trajectory that has brought him to the forefront of stem-cell research (see also Dr Willam Reville's column, right).
These discoveries encouraged him to leave his native Cork to pursue scientific studies abroad after completing a BSc in Cork and a MSc in Trinity.
"I left because of two big scientific discoveries. One was the cloning of Dolly the sheep," says Sullivan. "I was interested because you could artificially make a cell forget what it once was.
"The other discovery was isolating human embryonic stem-cells. I realised I couldn't do this research in Ireland so I had to leave."
Dr Sullivan is a researcher in the Harvard Stem Cell Institute, a centre established in 2004 that involves the work of more than 300 scientists. He studies various aspects of stem cells, including their capacity to contribute to the detailed study of disease and in new drug discovery.
When he left Ireland in 1998 he went straight to one of the epicentres of advanced genetic research, the Roslin Institute in Edinburgh, where Ian Wilmut and colleagues had created Dolly, the first large mammal clone. "I put on my belligerent Corkman hat and argued my way into Roslin," Dr Sullivan says.
He completed a PhD there before moving first to Cambridge and then on to Harvard in Boston where he specialises in the reprogramming of ordinary cells into stem-cells. "I am trying to isolate the factors that support reprogramming," he explains.
He is also studying specific applications of stem cells in the support of research. "I am involved in using human pluripotent stem cells for a range of applications, for example drug screening and disease modelling."
Drug studies involve using in vitro cell cultures to assess response to potential new drugs. "If you are looking for a drug say for Parkinson's you either use skin cells or transformed cells," he says. Transformed cells are "analogous to cancerous cells" and so are not an ideal cell type for this purpose. Nor are skin cells.
"We are using the pluripotent stem cells for making neurons or other cell types that will be more (stable) like the cells you could get from a patient. You have better new cell material to test your drugs on," Sullivan explains.
Stem cells and the cell types they can produce are also proving a powerful technology in disease modelling. It involves culturing two batches of cells, one completely normal and one from a patient where a disease is present.
These are grown on and the researchers can watch gene expression and other molecular aspects in enormous detail, watching for differences that emerge over time, he explains.
"That gives you a clue to what steps are involved in the very early stages of a disease," he says. Diabetes is an example of a disease that is "getting a lot of attention" in the Harvard institute.
Skin cells are first reprogrammed to become pluripotent stem cells and these in turn are transformed into pancreatic progenitor cells. Cells cultured from a patient with diabetes will carry with them a genetic predisposition for the disease, so a diseased condition should emerge from these cells.
The gene expression in the cells can be compared with a matching culture where there is no disease present. It also means researchers can track the steps which gradually allow disease to emerge.
Dr Sullivan believes the approach may yield medical advances more quickly than the traditional hope for stem cells in diabetes, the growing of tissues to replace the lost insulin-producing cells. "As a basic research tool, these pluripotent stem-cells are here and now and can be used here and now," he states.
The institute is also studying Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. It causes the gradual death of motor neurons, causing serious loss of motor control and possible paralysis. The Harvard group established a link between the loss of neurons seen in ALS and another cell type in the brain, glial cells. "The glial cells were at fault. This wasn't known before," Dr Sullivan states. The work involved cell culturing methods involving stem cells.