When everyone started getting excited about the remarkable potential offered by RNAi back in the late nineties, there were a couple of people out there who foresaw that a few problems needed to be ironed out before the stampede began.

One of those was Professor Bryan Williams, a cancer biologist who along with colleagues had been looking closely at certain enzymatic pathways and RNA-protein interactions.

Like many, Williams realised that while RNAi was going to become an incredibly powerful tool, the synthetic siRNAs being developed to mimic the process might not be as specific as some claimed. In fact, many believed that siRNAs could activate the innate immune system.

Williams and colleagues gained a certain amount of "notoriety", as he puts it, when these doubts were first published.

"Initially it was propagated by leaders in the field that RNAi would not activate some of the intracellular enzymatic pathways that myself and colleagues had worked on for many years," Williams says.

"But we thought we knew better because we understood the details of these RNA-protein interactions. And while they claimed short interfering RNAs would not be able to activate these enzymatic pathways, we in fact showed that they did. We spent a good deal of time trying to figure out the mechanism.

"We now know that siRNAs can activate protein kinase R (PKR) but more importantly, we think that in the circumstances where you get major cytokine production, they also activate an intracellular helicase called RIG-I. And they are also able to activate specific toll-like receptors."

Williams has been studying the molecular biology of cancers for many years, including a decade at the Hospital for Sick Children in Toronto and 15 years as chairman of the department of cancer biology at the Lerner Research Institute in Cleveland.

This provided a great opportunity to lead a new department and to build a multi-disciplinary team, including basic research scientists and surgeons and physicians who were running research labs as well as treating patients.

Williams is well known for his research into Wilms' tumour, a nephroblastoma that primarily affects children, and in the molecular biology of tumour suppression, particularly the role that tumour suppressor genes may play in regulating cell growth, maturation and apoptosis.

The role of innate immunity in cancer and other diseases has also made up a large part of his research career. In particular, he and his colleagues have made major steps in the understanding of how signalling pathways are activated by interferons and other cytokines in response to extracellular stimuli.

He became involved in RNAi research a little by accident, he says.

"We were looking at adopting antisense technology for a very long time and in fact had set up a small biotech company in Cleveland to exploit that. But RNA interference came along and we took a look at what we were doing and thought, this is where things are going to be moving very quickly.

"I'd always been interested in RNA-protein interaction and I wondered a little about the specificity of RNA interference. I was concerned that perhaps it wasn't as specific as it was made out to be and that turned out to be the case.

"We achieved some notoriety with some of our first publications in that area, but we showed that although RNAi can be incredibly specific and can target disease-causing genes, it also has non-specific effects on the innate immune system."