Of mice and human genomes

It's something of a mystery how drugs work in the human body. Taking an aspirin to cure your headache may get rid of the pain but what side-effects does the drug produce, you may wonder? Doctors and scientists, too, are continually querying how certain medicines and treatments affect us. The recent launch of a research collaboration - the Biopharmaceutical Sciences Network (which will integrate research being carried out by the country's leading universities and experts) - promises to throw new light on what was, up to now, a shadowy area of medical practice.

Its forerunner was the Institute of Biopharmaceutical Sciences, a clinical research centre based in Beaumont Hospital whose mission was to "better understand how drugs work in man", explains Professor Des Fitzgerald, clinical pharmacologist at the Royal College of Surgeons in Ireland, where the new centre will be based.

The new facility was funded by the Higher Education Authority at a cost of £8.7 million. It will provide technological support for a number of research programmes already being undertaken by Institute members into, for example, cardiovascular disease such as coronary thrombosis; cystic fibrosis, being carried out by Professor McElvaney at Beaumont Hospital; and investigations into neuropharmacology (how drugs work on the brain and neural tissue), which is of particular interest to the RCSI's Professor John Waddington in his studies into schizophrenia.

"I think one key thing to remember is that all the technology that has been developed worldwide at the moment and the description of the human genome is going to provide a whole series of new diagnostic and therapeutic tools," says Prof Fitzgerald.

The "biggest roadblock" for researchers, he adds, is the time it takes (up to 14 years) and the cost (about £350 million) to process a drug from its inception to the time when it can be given to a patient.

Delays occur because, for every drug which is introduced, thousands of patients have to be studied: "We believe that if we became more sophisticated in what we are doing we would get better clues using good technology at an early stage in fewer individuals and decide whether or not a drug should go forward or, actually more importantly, who should receive the drug. That's what this technology, I think, is going to be able to do."

IN the future, he predicts, drugs will become "much cleaner" and better targeted at disease, as researchers come to grips with identifying the proteins in the human body, of which, it is estimated, there are "probably a million". Patient care, therefore, will also improve, he adds. "The way that will happen is that we now know all the genes that are present in humans and one of the big projects that we will be part of in the next five years will be translating all those genes into proteins because proteins are what drugs are targeted against. Once all the proteins have been described and are available to work on, then we can start looking to see what are the drugs which actually interact with them." Transgenics, which looks at the effects of introducing or removing a gene in rodents, is another area of interest for researchers and is, according to Prof Fitzgerald, "a powerful tool in drug discovery".

The mouse and the human genome, he says, contain a lot of important parallels, and can provide useful models for study. There are, for example, around 60,000 people in Ireland every year who become blind because of the degeneration of the eye nerves.

TCD's Professor Peter Humphreys is currently investigating therapies for this condition. "If you want to develop a therapy", explains Prof Fitzgerald, "you have to have a model of it. You don't want to go straight into patients - that wouldn't be feasible. So this sort of technology where you can develop the model and, therefore, choose a suitable treatment in the model before you go into humans. . . I think this is the key technology in the future."

The network will team up with UCC Professors Fergus Shanahan and Gerry O'Sullivan on their studies into colon cancer, a disease which affects 5 per cent to 7 per cent of our population. There is a strong hereditary element to this illness, says Prof Fitzgerald, and the research is aimed at finding the gene which is causing the disease.

Looking to the future, he foresees the new network being able to undertake more in-depth and focused research. "What's happening is that the technology is so generic that it can be applied anywhere," he says. "All laboratories are going in the same direction and, eventually, there is no distinction between what I do as a clinical pharmacologist and what somebody is doing as a microbiologist. We're all using the same technology, so it forms a very good platform for developing research within the institution."