Changing of the guard at Merck

Emeritus Professor Graham Macdonald had a rather pleasant time at his recent Festschrift, held at the University of New South Wales in March to celebrate 30 years as an academic nephrologist and more recently as coordinator for external licensing with Merck. Not that anyone misbehaved - he just thought "it could possibly have been one of those parties that no one comes to, but it didn't turn out that way".

The Festschrift was a fitting tribute to a scientist who has become one of Australia's most esteemed. After a long career in research and teaching, in 1998 he joined Merck as medical director and took up the external licensing job in 2001.

Over his years in research, Macdonald has made a significant contribution to science, particularly in identifying, with colleague Karen Duggan, the roles of gut hormones in renal sodium excretion and metabolism and how angiotensin-converting enzyme inhibitors work.

With Stephen MacMahon he uncovered important links between obesity and high blood pressure, together showing that losing weight was as effective in treating high blood pressure as beta-blockers. With Brian Oldenburg he worked on helping people on kidney dialysis, who are unable to tolerate a normal load of water, contain their thirst. They worked out the principal factors in thirst, especially the role of the hormone angiotensin II.

So after many years as a researcher and a teacher, why did he go over to the dark side? "First of all I wanted a challenge - I hadn't done anything like it before," he says. "Also, I thought what could I do to help Merck? You can't do it from the outside; you have to do it from the inside."

Creating the position of external licensing coordinator was a collective decision, he says. "We were looking for ways to innovate better in Australian medical research. We had had a medical research foundation that we thought went very well but we looked for another way that we could do something useful in smoothing out the channels of communication between Australian science and Merck.

"We set in train a system where we went and visited every research lab and biotechnology company in Australia over a period of about six months and then set ourselves a schedule to get back there every two to three years, which we did. The system within Merck for capturing what [researchers] were doing was vastly improved."

Judging what exactly would make a good collaboration for Merck is a lot easier now, he says. The company established a six-monthly publication of various areas of interest, including detailed drug targets as well as pointing out areas it isn't particularly interested in. It has a detailed monthly list of areas of interest, wants and needs to refer to and a searchable database.

Those areas of interest are obvious, he says. "Metabolic disease - diabetes, obesity, arthrosclerosis are always going to be very important. Cancer in general - there is a whole new era of cancer pharmaceuticals coming up, and the other one is chronic neurological disease. Also neuro-repair and neuro-preservation - preserving nerve function and nerve cells after stroke is a really major target.

"That's not to say we are not interested in a whole heap of other things, we are, it's just that we have set a list of priorities and if you are in the really hot areas the threshold for interest is low. If you get into things that we regard as less critical then we need more data."

The long haul

Macdonald is taking the next two months off completely before deciding what level of involvement he will keep in the research and commercial sector in future. "I'm going to try to be properly retired - I will be applying a steely self-resolve," he says. He has spent the last several months handing over to his successor, Phil Kearney, whom he says will take the job of talent scout to a whole new level.

Kearney is well-known in Australian research. He did his PhD in Pseudomonas aeruginosa genetics at Monash with Bruce Holloway, went to London to work in the lab that was mapping the Y chromosome and then returned to Melbourne to work with David Danks at the Murdoch Institute, this time mapping the X. He then headed to Sydney, where he spent over a decade as head of the St Vincent's Hospital haematology research laboratory.

Biotech then tempted him and he moved to Sweden for five years to work with ActiveBiotech as head of its cancer division, and then on to Danish company Santaris Pharma to work in antisense. When MSD came looking for him, the offer was far too good to refuse, he says. Now, he is looking forward to trying to fill Macdonald's rather large shoes.

"Obviously I have to build on his success," Kearney says. "He has a wonderful network and I've been amazed at how well Merck is held in regard here - it's a lot of things but Graham has certainly contributed to that. I hope that having a bit of a stronger science background will help us to be a bit more expansive about what we bring in and to identify things a bit more easily that fit with Merck."

Those things are the big ones that Macdonald mentioned - Alzheimer's, neurodegeneration, obesity, diabetes and oncology. "We'd like to emphasise the amount of interest there is in Australian research from big pharma," Kearney says. "There is a great deal of interest from Merck and we are also positioned to try and remedy interest in science as a career, through interaction with schools and through scholarships, postdoctoral training, career development et cetera. And we are in for the long haul - we don't just run in, grab the prize and run away."

And if another Gardasil comes up? "That might be a little too much to hope for," he says. "If I can actually pick one project that gets up and turns into a Gardasil, I'd be very happy."