Recorded: 15 Jan 2003
One of my close colleagues at the time was Walter Keller, who was a visitor to Cold Spring Harbor. He was actually an employee of Cold Spring Harbor for a long time. But like many people that leave Cold Spring Harbor he became a visitor—almost an annual visitor. He was an expert in enzymology and once splicing had been discovered we all, of course, realized that there must be enzymatic machinery that accomplishes that process. And Walter Keller was a person that if anyone as we thought could undertake a study of enzymatic processes involved in RNA splicing it would be Walter Keller. He was very, very enthusiastic and came back and worked in Joe’s lab in collaboration with me and we started to search for the so-called splicing enzyme at that time.
And I remember a very exciting period when in fact we thought that we had splicing enzyme. We had some evidence for its existence using an invitro system that Walter and I had established. And it was so exciting that we had to decide whether or not to present this. It was an experiment done once and I had an opportunity to go along to a Keystone symposium and present this data. And I remember again a conversation with Jim Watson on Bungtown Road when we discussed whether or not it was appropriate to talk about something that really was very preliminary. And our instinct was to not do so until we had substantiated the claim in the traditional way which was to repeat it two or three times. And the decision helped along by advice from Jim Watson was that we would take a chance and go along and talk about this, and I did so and gave I think a nice talk at the Keystone conference there and it went down very, very well and I left people thinking that we had in fact identified a splicing enzyme and were on the way to tracking it down.
It turned out, I’m very sorry to say, to be an artifact. And is one of those things that haunted Walter Keller and I for a few months. In our mind’s eye at least started to think we would become famous as the guys that claimed to have the splicing enzyme only to realize that we did not. I think we probably, over a period of time, were able to dismiss that and we each went on and did slightly different things and resurrected our careers again, but that was an awkward moment. And to this day it’s not entirely clear what the basis of the artifact was. Other people subsequently have gone on and made the discovery. But it was an awkward time, although a very exciting time at the moment.
Walter and I continued to work on that project for several months following that and we worked on it at fever pitch. Walter and I were a good mix because he was an enzymologist and I was more of a virologist so I was the producer of the substrate that we were going to use to try and test enzymatic activity on. And we tried that seven or eight times. The reason for that is that we’d seen it once, seen what we thought was a positive result once, and were trying to reproduce that. I think had we not got that positive result we would have done the traditional thing which is to try something two or three times and had it not worked we would have abandoned it.
Well, we eventually did abandon it and I moved on to something quite different and left Cold Spring Harbor, but feeling that it had been a wonderful time and experience for me there and went on and did something entirely different. –
Ashley Dunn is currently a Senior Consulting Scientist and member of the Scientific Advisory Board at the Cryptome Pharmaceuticals Ltd., an Australian biotech company. He also serves on Australia’s Gene Technology Advisory Committee. He is the former Head of Molecular Biology in the Melbourne Branch of the Ludwig Institute for Cancer Research.
He came to Cold Spring Harbor Laboratory in 1976 to work with Joe Sambrook as a postdoctoral fellow and eventually became a junior faculty member.
His research has been concentrated on mammalian growth factors and the regulators responsible for the production of white blood cells in mice and men. He co-invented a mammalian blood cell regulator (GM-CSF), and his lab was the one of the first to establish gene targeting in the development of human diseases such as cancer.